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2016
Dalton Wamalwa, Benki-Nugent S, Langat A, Tapia K, Ngugi E, Moraa H, Maleche-Obimbo E, Otieno V, Inwani I, Richardson BA, Chohan B, Overbaugh J, John-Stewart GC. "Treatment interruption after 2-year antiretroviral treatment (ART) initiated during acute/early HIV in infancy: a randomized trial." AIDS. 2016. Abstract

Treatment interruption (TI) has been safe and durable in some pediatric studies but none have compared TI to continued antiretroviral treatment (ART) following ART initiation in early HIV. The objective of this study was to compare outcomes in TI versus continued ART among early-treated infants.

Mecha JO, Kubo EN, Nganga LW, Muiruri PN, Njagi LN, Mutisya IN, Odionyi JJ, Ilovi SC, Wambui M, Githu C, Ngethe R, Obimbo EM, Ngumi ZW. "Trends in clinical characteristics and outcomes of Pre-ART care at a large HIV clinic in Nairobi, Kenya: a retrospective cohort study." AIDS Res Ther. 2016;13:38. Abstract

The success of antiretroviral therapy in resource-scarce settings is an illustration that complex healthcare interventions can be successfully delivered even in fragile health systems. Documenting the success factors in the scale-up of HIV care and treatment in resource constrained settings will enable health systems to prepare for changing population health needs. This study describes changing demographic and clinical characteristics of adult pre-ART cohorts, and identifies predictors of pre-ART attrition at a large urban HIV clinic in Nairobi, Kenya.

2015
Ásbjörnsdóttir KH, Slyker JA, Maleche-Obimbo E, Dalton Wamalwa, Phelgona Otieno, Grace C. John-Stewart, Gichuhi CM, John-Stewart G. "Breastfeeding Is Associated with Decreased Risk of Hospitalization among HIV-Exposed, Uninfected Kenyan Infants." J Hum Lact. 2015. Abstract

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.

Jonnalagadda S, LaCourse SM, Otieno P, Lohman-Payne B, Maleche-Obimbo E, Cranmer LM, John-Stewart GC. "Incidence and correlates of tuberculosis IGRA conversion among HIV-infected postpartum women." Int. J. Tuberc. Lung Dis.. 2015;19(7):792-8. Abstract

Prevention of maternal-to-child transmission program at a tertiary care hospital in Nairobi, Kenya. The risk of acquiring Mycobacterium tuberculosis infection among peripartum human immunodeficiency virus (HIV) infected women is poorly defined.

Maleche-Obimbo E, Wanjau W, Kathure I. "The journey to improve the prevention and management of childhood tuberculosis: the Kenyan experience." Int. J. Tuberc. Lung Dis.. 2015;19 Suppl 1:39-42. Abstract

Child tuberculosis (TB) cases in Kenya, a high TB burden country, constitute more than one tenth of all TB cases. This paper describes Kenya's efforts in the past decade to increase awareness about policy, improve leadership and combat the multiple challenges faced in the diagnosis and management of children presumed to have TB. We describe the increasing advocacy and involvement of paediatricians and the child health sector with the National TB Programme, and the resulting improvement in leadership, policy, child-specific guidelines and training materials, health worker capacity, and the implementation of prevention and cure of child TB.

Chohan BH, Tapia K, Benki-Nugent S, Khasimwa B, Ngayo M, Maleche-Obimbo E, Dalton Wamalwa, Overbaugh J, John-Stewart G. "Nevirapine Resistance in Previously Nevirapine-Unexposed HIV-1-Infected Kenyan Infants Initiating Early Antiretroviral Therapy." AIDS Res. Hum. Retroviruses. 2015;31(8):783-91. 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-antiretroviral therapy (ART), the development and impact of NVP resistance have 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, seven (37%) infants developed resistance: one at 3 months and six at 6 months after ART initiation. The 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 the 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. The development of NVP resistance may, in part, explain the superiority of protease inhibitor-based ART in infants.

Agweyu A, Gathara D, Oliwa J, Muinga N, Edwards T, Allen E, Maleche-Obimbo E, English M. "Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial." Clin. Infect. Dis.. 2015;60(8):1216-24. Abstract

There are concerns that the evidence from studies showing noninferiority of oral amoxicillin to benzyl penicillin for severe pneumonia may not be generalizable to high-mortality settings.

2014
Njuguna IN, Ambler G, Reilly M, Ondondo B, Kanyugo M, Lohman-Payne B, Christine Gichuhi, Dalton Wamalwa, Borthwick N, Black A, Mehedi S-R, Sun J, Maleche-Obimbo E, Chohan B, John-Stewart GC, Jaoko W, Hanke T. "PedVacc 002: a phase I/II randomized clinical trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi." Vaccine. 2014;32(44):5801-8. Abstract

A safe, effective vaccine for breastfeeding infants born to HIV-1-positive mothers could complement antiretroviral therapy (ART) for prevention of mother-to-child transmission of HIV-1. To date, only a few HIV-1 vaccine candidates have been tested in infants.

Beima-Sofie K, John-Stewart G, Shah B, Dalton Wamalwa, Maleche-Obimbo E, Kelley M. "Using health provider insights to inform pediatric HIV disclosure: a qualitative study and practice framework from Kenya." AIDS Patient Care STDS. 2014;28(10):555-64. 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.

Agweyu A, Kibore M, Digolo L, Kosgei C, Maina V, Mugane S, Muma S, Wachira J, Waiyego M, Maleche-Obimbo E. "Prevalence and correlates of treatment failure among Kenyan children hospitalised with severe community-acquired pneumonia: a prospective study of the clinical effectiveness of WHO pneumonia case management guidelines." Trop. Med. Int. Health. 2014;19(11):1310-20. Abstract

To determine the extent and pattern of treatment failure (TF) among children hospitalised with community-acquired pneumonia at a large tertiary hospital in Kenya.

Gasper MA, Kunwar P, Itaya G, Lejarcegui N, Bosire R, Maleche-Obimbo E, Dalton Wamalwa, Slyker J, Overbaugh J, Horton H, Sodora DL, John-Stewart G, Lohman-Payne B. "Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection." AIDS. 2014;28(8):1115-24. Abstract

To determine neonatal immunologic factors that correlate with mother-to-child-transmission of HIV-1.

Mutinda CM, Onyango FE, Maleche-Obimbo E, Kumar R, Wamalwa D, Were F, Osano B, Mburugu P. "ADHERENCE TO PNEUMONIA GUIDELINES FOR CHILDREN 2 - 59 MONTHS AT GARRISA PROVINCIAL GENERAL HOSPITAL." East Afr Med J. 2014;91(1):13-20. Abstract

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%.

Cranmer LM, Kanyugo M, Jonnalagadda SR, Lohman-Payne B, Sorensen B, Elizabeth Maleche Obimbo, Dalton Wamalwa, John-Stewart GC. "High Prevalence of Tuberculosis Infection in HIV-1 Exposed Kenyan Infants." Pediatr. Infect. Dis. J.. 2014;33(4):401-6. 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 bacille Calmette-Guérin (BCG) vaccination, TB interferon gamma release assays (IGRAs) do not cross-react with BCG and enable detection of TB infection in infancy.

Cranmer LM, Kanyugo M, Jonnalagadda SR, Lohman-Payne B, Sorensen B, Elizabeth Maleche Obimbo, Dalton Wamalwa, John-Stewart GC. "High prevalence of tuberculosis infection in HIV-1 exposed Kenyan infants." Pediatr. Infect. Dis. J.. 2014;33(4):401-6. 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 bacille Calmette-Guérin (BCG) vaccination, TB interferon gamma release assays (IGRAs) do not cross-react with BCG and enable detection of TB infection in infancy.

Slyker JA, Patterson J, Ambler G, Richardson BA, Maleche-Obimbo E, Bosire R, Mbori-Ngacha D, Farquhar C, John-Stewart G. "Correlates and outcomes of preterm birth, low birth weight, and small for gestational age in HIV-exposed uninfected infants." BMC Pregnancy Childbirth. 2014;14:7. Abstract

Preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) contribute to neonatal mortality. Maternal HIV-1 infection has been associated with an increased risk of PTB, but mechanisms underlying this association are undefined. We describe correlates and outcomes of PTB, LBW, and SGA in HIV-exposed uninfected infants.

Newman LP, Njoroge A, Ben-Youssef L, Merkel M GA, Ton Q, Obimbo EM WD, Lohman-Payne B, Nduati R, Obimbo E. "Measles Seropositivity in HIV-Infected Kenyan Children on Antiretroviral Therapy." Pediatr Infect Dis J. 2014 Mar 10. [Epub ahead of print] PMID: 24618938 [PubMed - as supplied by publisher] . 2014. Abstract

1. Pediatr Infect Dis J. 2014 Mar 10. [Epub ahead of print]

Measles Seropositivity in HIV-Infected Kenyan Children on Antiretroviral Therapy.

Newman LP(1), Njoroge A, Ben-Youssef L, Merkel M, Gatuguta A, Ton Q, Obimbo EM,
Wamalwa D, Lohman-Payne B, Richardson BA, Nduati R, Farquhar C.

Author information:
(1)a Department of Epidemiology, c Department of Medicine, g Department of Global
Health, e Department of Biostatistics, University of Washington, Seattle, WA, USA
b Department of Public Health, d Department of Paediatrics and Child Health,
University of Nairobi, Nairobi, Kenya f Division of Vaccine and Infectious
Disease, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

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.

PMID: 24618938 [PubMed - as supplied by publisher]

2013
Beima-Sofie KM, Bigham AW, Lingappa JR, Dalton Wamalwa, Mackelprang RD, Bamshad MJ, Maleche-Obimbo E, Richardson BA, John-Stewart GC. "Toll-like receptor variants are associated with infant HIV-1 acquisition and peak plasma HIV-1 RNA level." AIDS. 2013;27(15):2431-9. Abstract

We evaluated the association of single nucleotide polymorphisms (SNPs) in TLRs with infant HIV-1 acquisition and viral control.

Beima-Sofie KM, Bigham AW, Lingappa JR, Dalton Wamalwa, Mackelprang RD, Bamshad MJ, Maleche-Obimbo E, Richardson BA, John-Stewart GC. "Toll-like receptor variants are associated with infant HIV-1 acquisition and peak plasma HIV-1 RNA level." AIDS. 2013;27(15):2431-9. Abstract

We evaluated the association of single nucleotide polymorphisms (SNPs) in TLRs with infant HIV-1 acquisition and viral control.

Ásbjörnsdóttir KH, Slyker JA, Weiss NS, Mbori-Ngacha D, Maleche-Obimbo E, Dalton Wamalwa, John-Stewart G. "Breastfeeding is associated with decreased pneumonia incidence among HIV-exposed, uninfected Kenyan infants." AIDS. 2013;27(17):2809-15. Abstract

HIV-exposed uninfected (HEU) infants have higher infectious disease morbidity and mortality than unexposed infants. We determined the incidence and risk factors for pneumonia, a leading cause of infant mortality worldwide, in a cohort of HEU infants. Identifying predictors of pneumonia among HEU infants may enable early identification of those at highest risk.

Wamalwa DC, Lehman DA, Benki-Nugent S, Gasper MA, Gichohi R, Maleche-Obimbo E, Farquhar C, John-Stewart GC, Overbaugh J. "Long-term virologic response and genotypic resistance mutations in HIV-1 infected Kenyan children on combination antiretroviral therapy." J. Acquir. Immune Defic. Syndr.. 2013;62(3):267-74. Abstract

HIV-infected children may require the use of combination antiretroviral treatment (cART) into adulthood. However, regimens are limited to first line and second line in many African settings. Therefore, understanding the long-term rate of virologic failure and drug resistance during prolonged antiretroviral treatment is important for establishing treatment strategies in African pediatric cohorts.

Slyker JA, Casper C, Tapia K, Richardson B, Bunts L, Huang M-L, Maleche-Obimbo E, Ruth Nduati, John-Stewart G. "Clinical and virologic manifestations of primary Epstein-Barr virus (EBV) infection in Kenyan infants born to HIV-infected women." J. Infect. Dis.. 2013;207(12):1798-806. Abstract

Human immunodeficiency virus (HIV) infection is a risk factor for Epstein-Barr virus (EBV)-associated lymphomas. Characterizing primary infection may elucidate risk factors for malignancy.

John-Stewart GC, Wariua G, Beima-Sofie KM, Richardson BA, Farquhar C, Maleche-Obimbo E, Mbori-Ngacha D, Dalton Wamalwa. "Prevalence, perceptions, and correlates of pediatric HIV disclosure in an HIV treatment program in Kenya." AIDS Care. 2013;25(9):1067-76. Abstract

Disclosure to HIV-infected children regarding their diagnosis is important as expanding numbers of HIV-infected children attain adolescence and may become sexually active. In order to define correlates of pediatric disclosure and facilitate development of models for disclosure, we conducted a cross-sectional survey of primary caregivers of HIV-1 infected children aged 6-16 years attending a pediatric HIV treatment program in Nairobi, Kenya. We conducted focus group discussions with a subset of caregivers to further refine perceptions of disclosure. Among 271 caregiver/child dyads in the cross-sectional survey, median child age was 9 years (interquartile range: 7-12 years). Although 79% of caregivers believed children should know their HIV status, the prevalence of disclosure to the child was only 19%. Disclosure had been done primarily by health workers (52%) and caregivers (33%). Caregivers reported that 5 of the 52 (10%) who knew their status were accidentally disclosed to. Caregivers of older children (13 vs. 8 years; p<0.001), who were HIV-infected and had disclosed their own HIV status to the child (36% vs. 4%; p=0.003), or who traveled frequently (29% vs. 16%, p=0.03) were more likely to have disclosed. Children who had been recently hospitalized (25% vs. 44%, p=0.03) were less likely to know their status, and caregivers with HIV were less likely to have disclosed (p=0.03). Reasons for disclosure included medication adherence, curiosity or illness while reasons for nondisclosure included age and fear of inadvertent disclosure. Our study found that disclosure rates in this Kenyan setting are lower than observed rates in the USA and Europe but consistent with rates from other resource-limited settings. Given these low rates of disclosure and the potential benefits of disclosure, strategies promoting health worker trainings and caregiver support systems for disclosure may benefit children with HIV.

Chohan BH, Tapia K, Merkel M, Kariuki AC, Khasimwa B, Olago A, Gichohi R, Obimbo EM, Wamalwa DC. "Pooled HIV-1 RNA Viral Load Testing for Detection of Antiretroviral Treatment Failure in Kenyan children.". 2013. Abstract

Pooled viral load (VL) testing with two different testing strategies was evaluated as a potential cost-saving method to monitor antiretroviral therapy (ART) in HIV-infected children receiving ART in a resource-limited setting. METHODS:: Archived samples collected from 250 HIV-1 infected children on first-line ART at various time-points post-ART initiation were evaluated for pooled VL testing using a minipool+algorithm strategy. Additionally, samples collected in real-time from 125 children on ART were assessed for virologic failure using a minipool strategy for pooled viral load testing. Virologic failure was determined as HIV-1 RNA viral loads >1500 copies/ml. RESULTS:: Minipool+algorithm strategy for pooled VL testing of archived samples had estimated viral failure of 13.6%, with a relative efficiency (RE) of 23.6% (95% CI; 18.5, 29.4), and negative predictive value (NPV) of 88%. This testing strategy would have resulted in 24% fewer assays needed, for a cost savings of $1,180 per 100 samples. The minipool strategy for pooled viral load testing of samples obtained in real-time yielded an estimated 23.2% of samples with viral failure and a RE of 8.0 % (95% CI; 3.9, 14.2); however had a minipool+algorithm pooling strategy been used the RE would increase to 20%. CONCLUSIONS:: The minipool+algorithm strategy for pooled VL testing to detect virologic failure in HIV-1 infected children on ART was determined to be relatively efficient in detecting virologic failure, had high NPV, with substantial cost savings. Pooling strategies may be important components of cost-effect strategies to reduce rates of viral failure and resistance, thus improving clinical outcomes.

2012
Wamalwa D, Lehman DA B-NGGSM, Benki-Nugent S, Gasper M GR, Maleche-Obimbo E, John-Stewart G OJ. " Long-term Virologic Response and Genotypic Resistance Mutations in HIV-1 Infected Kenyan Children on Combination Antiretroviral Therapy." J Acquir Immune Defic Syndr. 2012 Nov 28. [Epub ahead of print]. 2012. Abstract

Abstract
BACKGROUND:
HIV-infected children may require the use of combination antiretroviral treatment (cART) into adulthood. However, regimens are limited to first- and second-line in many African settings. Therefore, understanding the long-term rate of virologic failure and drug resistance during prolonged antiretroviral treatment is important for establishing treatment strategies in African pediatric cohorts.
METHODS:
Children ages 18 months to 12 years initiated first-line cART and were followed every 1-3 months, for up to 5.5 years. Treatment was switched to second-line based on clinical and immunologic criteria according to national guidelines. Virologic failure was determined retrospectively as defined by ≥2 viral loads >5000 copies/mL. Drug resistance was assessed during viral failure by population-based sequencing.
RESULTS:
Among 100 children on first-line cART followed for a median 49 months, 34% experienced virologic failure. Twenty-three (68%) of the 34 children with viral failure had detectable resistance mutations, of whom 14 (61%) had multi-class resistance. Fourteen (14%) children were switched to second-line regimens and followed for a median of 28 months. Retrospective analysis revealed that virologic failure had occurred a median of 12 months prior to the switch to second-line. During prolonged first-line treatment in the presence of viral failure, additional resistance mutations accumulated, however, only 1 (7%) of 14 children had persistent viremia during second-line treatment.
DISCUSSION:
Virologic suppression was maintained on first-line cART in two-thirds of HIV-infected children for up to 5 years. Switch to second-line based on clinical/immunologic criteria occurred ∼1 year after viral failure, but the delay did not consistently compromise second-line treatment.

Lohman-Payne B, Slyker JA MS, Maleche-Obimbo E, Richardson BA, Mbori-Ngacha D, Farquhar C O, Overbaugh J J-SG. "Breast milk cellular HIV-specific interferon γ responses are associated with protection from peripartum HIV transmission." AIDS. 2012 Oct 23;26(16):2007-16. doi: 10.1097/QAD.0b013e328359b7e0.. 2012. Abstract

Abstract
OBJECTIVE:
Breast milk is a major route of infant HIV infection, yet the majority of breast-fed, HIV-exposed infants escape infection by unknown mechanisms. This study aimed to investigate the role of HIV-specific breast milk cells in preventing infant HIV infection.
DESIGN:
A prospective study was designed to measure associations between maternal breast milk HIV-specific interferon-γ (IFN-γ) responses and infant HIV-1 detection at 1 month of age.
METHODS:
In a Kenyan cohort of HIV-infected mothers, blood and breast milk HIV-gag IFN-γ ELISpot responses were measured. Logistic regression was used to measure associations between breast milk IFN-γ responses and infant HIV infection at 1 month of age.
RESULTS:
IFN-γ responses were detected in breast milk from 117 of 170 (69%) women. IFN-γ responses were associated with breast milk viral load, levels of macrophage inflammatory protein (MIP) 1α, MIP-1β, regulated upon activation, normal T-cell expressed, and secreted and stromal-cell derived factor 1 and subclinical mastitis. Univariate factors associated with infant HIV infection at 1 month postpartum included both detection and breadth of breast milk IFN-γ response (P = 0.08, P = 0.04, respectively), breast milk MIP-1β detection (P = 0.05), and plasma (P = 0.004) and breast milk (P = 0.004) viral load. In multivariate analyses adjusting for breast milk viral load and MIP-1β, breast milk IFN-γ responses were associated with an approximately 70% reduction in infant HIV infection [adjusted odds ratio (aOR) 0.29, 95% confidence interval (CI) 0.092-0.91], and each additional peptide pool targeted was associated with an approximately 35% reduction in infant HIV (aOR 0.65, 95% CI 0.44-0.97).
CONCLUSION:
These data show breast milk HIV-gag-specific IFN-γ cellular immune responses are prevalent and may contribute to protection from early HIV transmission. More broadly, these data suggest breast milk cellular responses are potentially influential in decreasing mother-to-child transmission of viruses.

Diener LC, Slyker JA GC, Tapia KA, Richardson BA, Wamalwa D, Farquhar C, Overbaugh J, Maleche-Obimbo E, G. J-S. "Performance of the integrated management of childhood illness algorithm for diagnosis of HIV-1 infection among African infants. ." AIDS. 2012 Sep 24;26(15):1935-41. . 2012. Abstract

Abstract
OBJECTIVES:
Early infant HIV-1 diagnosis and treatment substantially improve survival. Where virologic HIV-1 testing is unavailable, integrated management of childhood illness (IMCI) clinical algorithms may be used for infant HIV-1 screening. We evaluated the performance of the 2008 WHO IMCI HIV algorithm in a cohort of HIV-exposed Kenyan infants.
METHODS:
From 1999 to 2003, 444 infants had monthly clinical assessments and quarterly virologic HIV-1 testing. Using archived clinical data, IMCI sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using virologic testing as a gold standard. Linear regression and survival analyses were used to determine the effect of age on IMCI performance and timing of diagnosis.
RESULTS:
Overall IMCI sensitivity, specificity, PPV, and NPV value were 58, 87, 52, and 90%, respectively. Sensitivity (1.4%) and PPV (14%) were lowest at 1 month of age, when 81% of HIV infections already had occurred. Sensitivity increased with age (P < 0.0001), but remained low throughout infancy (range 1.4-35%). Specificity (range 97-100%) was high at each time point and was not associated with age. Fifty-eight percent of HIV-1-infected infants (50 of 86) were eventually diagnosed by IMCI, and use of IMCI was estimated to delay diagnosis in HIV-infected infants by a median of 5.9 months (P < 0.0001).
CONCLUSION:
IMCI had low sensitivity during the first month of life, when the majority of HIV-1 infections had already occurred and initiation of treatment is most critical. Although sensitivity increased with age, the substantial delay in HIV-1 diagnosis using IMCI limits its utility in early infant HIV-1 diagnosis.

John-Stewart GC, Wariua G B-SKM, Richardson BA, Maleche-Obimbo E, Mbori-Ngacha D WD. "Prevalence, perceptions, and correlates of pediatric HIV disclosure in an HIV treatment program in Kenya." AIDS Care. 2012 Dec 20. [Epub ahead of print]. 2012. Abstract

Abstract
Abstract Disclosure to HIV-infected children regarding their diagnosis is important as expanding numbers of HIV-infected children attain adolescence and may become sexually active. In order to define correlates of pediatric disclosure and facilitate development of models for disclosure, we conducted a cross-sectional survey of primary caregivers of HIV-1 infected children aged 6-16 years attending a pediatric HIV treatment program in Nairobi, Kenya. We conducted focus group discussions with a subset of caregivers to further refine perceptions of disclosure. Among 271 caregiver/child dyads in the cross-sectional survey, median child age was 9 years (interquartile range: 7-12 years). Although 79% of caregivers believed children should know their HIV status, the prevalence of disclosure to the child was only 19%. Disclosure had been done primarily by health workers (52%) and caregivers (33%). Caregivers reported that 5 of the 52 (10%) who knew their status were accidentally disclosed to. Caregivers of older children (13 vs. 8 years; p<0.001), who were HIV-infected and had disclosed their own HIV status to the child (36% vs. 4%; p=0.003), or who traveled frequently (29% vs. 16%, p=0.03) were more likely to have disclosed. Children who had been recently hospitalized (25% vs. 44%, p=0.03) were less likely to know their status, and caregivers with HIV were less likely to have disclosed (p=0.03). Reasons for disclosure included medication adherence, curiosity or illness while reasons for nondisclosure included age and fear of inadvertent disclosure. Our study found that disclosure rates in this Kenyan setting are lower than observed rates in the USA and Europe but consistent with rates from other resource-limited settings. Given these low rates of disclosure and the potential benefits of disclosure, strategies promoting health worker trainings and caregiver support systems for disclosure may benefit children with HIV.

2011
Slyker JA, John-Stewart GC, Dong T, Lohman-Payne B, Reilly M, Atzberger A, Taylor S, Maleche-Obimbo E, Mbori-Ngacha D, Rowland-J. "Phenotypic Characterization of HIV-Specific CD8+ T Cells during Early and Chronic Infant HIV-1 Infection." BMC Infect Dis. 2011; 11: 259. Published online 2011 September 30. doi: 10.1186/1471-2334-11-259. 2011. Abstractphenotypic_characterization_of_hiv-specific_cd8.pdf

Abstract
Although CD8+ T cells play an important role in the containment of adult HIV-1 replication, their role in infant HIV-1
infection is not as well understood. Impaired HIV-specific CD8+ T cell responses may underlie the persistently high viral loads
observed in infants. We examined the frequency and phenotype of infant HIV-specific CD8+ T cells in 7 HIV-infected
antiretroviral therapy-naı¨ve infants during the first 2 years of life, using class I HLA tetramers and IFN-c-ELISPOT. The
frequency (0.088–3.9% of CD3+CD8+ cells) and phenotype (CD27+CD282, CD45RA+/2, CD57+/2, HLA-DR+, CD95+) of infant
HIV-specific CD8+ T cells were similar to reports in adults undergoing early infection. Unlike adults, at 23–24 months postinfection
a high frequency of HIV-specific CD8+ T cells expressed HLA-DR (mean 80%, range 68–85%) and CD95 (mean 88%,
range 79–96%), suggesting sustained activation and vulnerability to apoptosis. Despite comparable expansion of HIVspecific
CD8+ T cells of a similar phenotype to adults during early infection, infant T cells failed to contain HIV-1 replication,
and remained persistently activated and vulnerable to apoptosis during chronic infection.

Githinji N, Maleche-Obimbo E, Nderitu M, Wamalwa DC, Mbori-Ngacha D. "Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1 infected children in Kenya ." BMC Infectious Diseases. 2011. Abstractutility_of_total_lymphocyte_count.pdf

Abstract
Background: In resource-limited settings, such as Kenya, access to CD4 testing is limited. Therefore, evaluation of
less expensive laboratory diagnostics is urgently needed to diagnose immuno-suppression in children.
Objectives: To evaluate utility of total lymphocyte count (TLC) as surrogate marker for CD4 count in HIV-infected
children.
Methods: This was a hospital based retrospective study conducted in three HIV clinics in Kisumu and Nairobi in
Kenya. TLC, CD4 count and CD4 percent data were abstracted from hospital records of 487 antiretroviral-naïve HIVinfected
children aged 1 month - 12 years.
Results: TLC and CD4 count were positively correlated (r = 0.66, p < 0.001) with highest correlation seen in
children with severe immuno-suppression (r = 0.72, p < 0.001) and children >59 months of age (r = 0.68, p <
0.001). Children were considered to have severe immuno-suppression if they met the following WHO set CD4
count thresholds: age below 12 months (CD4 counts < 1500 cells/mm3), age 12-35 months (CD4 count < 750
cells/mm3), age 36-59 months (CD4 count < 350 cells/mm3, and age above 59 months (CD4 count < 200 cells/
mm3). WHO recommended TLC threshold values for severe immuno-suppression of 4000, 3000, 2500 and 2000
cells/mm3 for age categories <12, 12-35, 36-59 and >59 months had low sensitivity of 25%, 23%, 33% and 62%
respectively in predicting severe immuno-suppression using CD4 count as gold standard. Raising TLC thresholds to
7000, 6000, 4500 and 3000 cells/mm3 for each of the stated age categories increased sensitivity to 71%, 64%, 56%
and 86%, with positive predictive values of 85%, 61%, 37%, 68% respectively but reduced specificity to 73%, 62%,
54% and 68% with negative predictive values of 54%, 65%, 71% and 87% respectively.
Conclusion: TLC is positively correlated with absolute CD4 count in children but current WHO age-specific
thresholds had low sensitivity to identify severely immunosuppressed Kenyan children. Sensitivity and therefore
utility of TLC to identify immuno-suppressed children may be improved by raising the TLC cut off levels across the
various age categories.

2010
D.C W, E.M O, Farquhar C, Richardson BA, Mbori-Ngacha DA, Inwani I, Benki-Nugent S, G J-S. "1. Predictors of mortality in HIV-1 infected children on antiretroviral therapy in Kenya: a prospective cohort." BCM Pediatr. 2010:10-33.predictors_of_mortality_in_hiv-1infected_children.pdf
Jonnalagadda S, Barbara Lohman Payne, Elizabeth Brown, Dalton Wamalwa, Elizabeth Maleche Obimbo, Maxwel Majiwa, Carey. "Latent Tuberculosis Detection by Interferon g Release Assay during Pregnancy Predicts Active Tuberculosis and Mortality in Human Immunodeficiency Virus Type 1–Infected Women and Their Children." Journal of infectious diseases. 2010. Abstractlatent_tb_detection_by_interferon.pdf

Background. We evaluated the prognostic usefulness of interferon g release assays (IGRAs) for active tuberculosis
and mortality in Kenyan human immunodeficiency virus type 1 (HIV-1)–infected women and their infants.
Methods. Prevalence and correlates of Mycobacterium tuberculosis–specific T-SPOT.TB IGRA positivity were
determined during pregnancy in a historical cohort of HIV-1–infected women. Hazard ratios, adjusted for baseline
maternal CD4 cell count (aHRCD4), were calculated for associations between IGRA positivity and risk of active
tuberculosis and mortality over 2-year postpartum follow-up among women and their infants.
Results. Of 333 women tested, 52 (15.6%) had indeterminate IGRA results. Of the remaining 281 women,
120 (42.7%) had positive IGRA results, which were associated with a 4.5-fold increased risk of active tuberculosis
(aHRCD4, 4.5; 95% confidence interval [CI], 1.1–18.0; Pp.030). For immunosuppressed women (CD4 cell count,
!250 cells/mL), positive IGRA results were associated with increased risk of maternal mortality (aHRCD4, 3.5; 95%
CI, 1.02–12.1; ), maternal active tuberculosis or mortality (aHRCD4Pp.045 , 5.2; 95% CI, 1.7–15.6; Pp.004), and
infant active tuberculosis or mortality overall (aHRCD4, 3.0; 95% CI, 1.0–8.9; Pp.05) and among HIV-1–exposed
uninfected infants (aHRCD4, 7.3; 95% CI, 1.6–33.5; Pp.01).
Conclusions. Positive IGRA results for HIV-1–infected pregnant women were associated with postpartum
active tuberculosis and mortality among mothers and their infants.

2009
Slyker JA, Lohman-Payne BL, John-Stewart GC, Maleche-Obimbo E, Emery S, Richardson B, Dong T, Iversena AKN, Mbori-Ngacha DA, Overbaugh J, Rowland-Jones SL. "Acute cytomegalovirus infection in Kenyan HIV-infected infants.". 2009. AbstractWebsite

Objective: Cytomegalovirus (CMV) coinfection may influence HIV-1 disease progression
during infancy. Our aim was to describe the incidence of CMV infection
and the kinetics of viral replication in Kenyan HIV-infected and HIV-exposed uninfected
infants.
Methods: HIV-1 and CMV plasma viral loads were serially measured in 20 HIVexposed
uninfected and 44 HIV-infected infants born to HIV-infected mothers.
HIV-infected children were studied for the first 2 years of life, and HIV-exposed
uninfected infants were studied for 1 year.
Results: CMVDNAwas detected frequently during the firstmonths of life; by 3months of
age,CMVDNAwasdetectedin90%ofHIV-exposeduninfectedinfantsand93%of infants
whohadacquiredHIV-1inutero.CMVviral loadswerehighest inthe1–3monthsfollowing
the first detection of virus and declined rapidly thereafter. CMV peak viral loads were
significantlyhigher in theHIV-infectedinfantscomparedwith theHIV-exposeduninfected
infants (mean3.2versus2.7 log10CMVDNAcopies/ml, respectively,P¼0.03).Thedetection
of CMV DNA persisted to 7–9 months post-CMV infection in both the HIV-exposed
uninfected (8/17, 47%) and HIV-infected (13/18, 72%, P¼0.2) children. Among HIVinfected
children, CMV DNA was detected in three of the seven (43%) surviving infants
tested between 19 and 21 months post-CMV infection. Finally, a strong correlation was
found between peak CMV and HIV-1 viral loads (r¼0.40, P¼0.008).
Conclusion: Acute CMV coinfection is common in HIV-infected Kenyan infants. HIV-1
infection was associated with impaired containment of CMV replication.

Elizabeth R. Brown, Phelgona Otieno, Dorothy A. Mbori-Ngacha, Carey Farquhar, Elizabeth M. Obimbo, Ruth Nduati JO. "Comparison of CD4 Cell Count, Viral Load, and Other Markers for the Prediction of Mortality among HIV-1–Infected Kenyan Pregnant Women." J Infect Dis. 2009 May 1; . 2009;199(9): 1292–1300. doi:10.1086/597617. Abstractcomparison_of_cd4_cell_count_viral_load.pdf

Abstract
Background—There are limited data regarding the relative merits of biomarkers as predictors of
mortality or time to initiation of antiretroviral therapy (ART).
Methods—We evaluated the usefulness of the CD4 cell count, CD4 cell percentage (CD4%), human
immunodeficiency virus type 1 (HIV-1) load, total lymphocyte count (TLC), body mass index (BMI),
and hemoglobin measured at 32 weeks’ gestation as predictors of mortality in a cohort of HIV-1–
infected women in Nairobi, Kenya. Sensitivity, specificity, positive predictive value (PPV), and area
under the receiver operating characteristic (ROC) curve (AUC) were determined for each biomarker
separately, as well as for the CD4 cell count and the HIV-1 load combined.
Results—Among 489 women with 10,150 person-months of follow-up, mortality rates at 1 and 2
years postpartum were 2.1% (95% confidence interval [CI], 0.7%–3.4%) and 5.5% (95% CI, 3.0%–
8.0%), respectively. CD4 cell count and CD4% had the highest AUC value (>0.9). BMI, TLC, and
hemoglobin were each associated with but poorly predictive of mortality (PPV, <7%). The HIV-1
load did not predict mortality beyond the CD4 cell count.
Conclusions—The CD4 cell count and CD4% measured during pregnancy were both useful
predictors of mortality among pregnant women. TLC, BMI, and hemoglobin had a limited predictive
value, and the HIV-1 load did not predict mortality any better than did the CD4 cell count alone.
In 2007, >85% of the world’s estimated 2 million HIV-infected pregnant women lived in sub-
Saharan Africa [1]. Many women in this region have HIV-1 infection diagnosed during
pregnancy as part of programs designed to prevent mother-to-child transmission of HIV-1
(PMTCT). Within these programs for the prevention of mother-to-child transmission of HIV-1,

Wamalwa DC, Farquhar C, Obimbo EM, Selig S, Mbori-Ngacha DA, et al. "Medication diaries do not improve outcomes with highly active antiretroviral therapy in Kenyan children: a randomized clinical trial ." Journal of the International AIDS Society Research. 2009. Abstractmedication_diaries_do_not_improve_outcomes.pdf

Abstract
Background: As highly active antiretroviral therapy (HAART) becomes increasingly available to African children,
it is important to evaluate simple and feasible methods of improving adherence in order to maximize benefits of
therapy.
Methods: HIV-1-infected children initiating World Health Organization non-nucleoside reverse transcriptaseinhibitor-
containing first-line HAART regimens were randomized to use medication diaries plus counselling, or
counselling only (the control arm of the study). The diaries were completed daily by caregivers of children
randomized to the diary and counselling arm for nine months. HIV-1 RNA, CD4+ T cell count, and z-scores for
weight-for-age, height-for-age and weight-for-height were measured at a baseline and every three to six months.
Self-reported adherence was assessed by questionnaires for nine months.
Results: Ninety HIV-1-infected children initiated HAART, and were followed for a median of 15 months
(interquartile range: 2–21). Mean CD4 percentage was 17.2% in the diary arm versus 16.3% in the control arm at
six months (p = 0.92), and 17.6% versus 18.9% at 15 months (p = 0.36). Virologic response with HIV-1 RNA of
<100 copies/ml at nine months was similar between the two arms (50% for the diary arm and 36% for the control,
p = 0.83). The weight-for-age, height-for-age and weight-for-height at three, nine and 15 months after HAART
initiation were similar between arms. A trend towards lower self-reported adherence was observed in the diary
versus the control arm (85% versus 92%, p = 0.08).
Conclusion: Medication diaries did not improve clinical and virologic response to HAART over a 15-month
period. Children had good adherence and clinical response without additional interventions. This suggests that
paediatric HAART with conventional counselling can be a successful approach. Further studies on targeted
approaches for non-adherent children will be important.

Elizabeth Maleche Obimbo MBCB, et al. "Pediatric HIV-1 in Kenya: Pattern and Correlates of Viral Load and Association With Mortality ,." J Acquir Immune Defic Syndr. 2009. Abstractpediatric_hiv-1_in_kenya.pdf

Abstract
Background—There is limited information regarding the pattern and correlates of viral replication
in vertically HIV-1–infected children and its role on their outcomes in resource-limited settings.
Methods—HIV-1–infected infants were followed from birth to 24 months. Serial HIV-1 RNA
levels were compared in infants infected in utero (<48 hours), peripartum (48 hours–1 month), and
late postnatal (after 1 month). Cofactors for viral peak [highest viral load (VL) within 6 months of
infection] and set point and mortality were determined.
Results—Among 85 HIV-1–infected infants, 24 were infected in utero, 41 peripartum, 13 late
postnatal; 7 had no 48-hour assay. HIV-1 VL set point was significantly lower in infants infected >1
month vs. ≤1 month (5.59 vs. 6.24 log10 copies per milliliter, P = 0.01). Maternal VL correlated with
peak infant VL (P < 0.001). Univariately, infant peak and set point VL and 6-month CD4% <15%
predicted mortality; and 6-month CD4% <15% remained independently predictive in multivariate
analyses (hazard ratio = 4.85, 95% confidence interval: 1.90 to 12.36).
Conclusions—Infants infected after the age of 1 month contained virus better than infants infected
before 1 month of age. Maternal VL predicted infant VL, which, in turn was associated with early
mortality.

Inwani I, Mbori-Ngacha DA, R W Nduati, Obimbo E, Dalton Wamalwa, John-Stewart G, Farquhar C. "Performance of Clinical Algorithms for HIV-1 Diagnosis and Antiretroviral Initiation among HIV-1-Exposed Children Aged Less Than 18 Months in Kenya.". 2009. Abstract

Ninety percent of HIV-1-infected children live in sub-Saharan Africa. In the absence of diagnosis and antiretroviral therapy (ART), approximately 50% die before 2 years. Methods We evaluated sensitivity and specificity of clinical algorithms for diagnosis of HIV-1 infection and ART initiation among HIV-1-exposed children aged less than 18 months. Children were identified with routine HIV-1 testing and assessed using 3 sets of criteria: 1) Integrated Management of Childhood Illnesses (IMCI), 2) World Health Organization Presumptive Diagnosis (WHO-PD) for HIV-1 infection, and 3) CD4 T-lymphocyte cell subsets. HIV-1 infection status was determined using DNA PCR testing. Findings A total of 1,418 children (median age 5.4 months) were screened for HIV-1 antibodies, of whom 144 (10.2%) were seropositive. Of these, 134 (93%) underwent HIV-1 DNA testing and 80 (60%) were found to be HIV-1-infected. Compared to HIV-1 DNA testing, sensitivity and specificity of the IMCI were 19% and 96% and for WHO-PD criteria 43% and 88%, respectively. Inclusion of severe immune deficiency determined by CD4 percent improved sensitivity of IMCI and WHO-PD to 74% and 84% respectively, however, specificity declined to 43% and 41%, respectively. Interpretation Diagnosis of HIV-1 infection among exposed children less than 18 months in a high prevalence, resource-limited setting remains a challenge and current recommended algorithms have low sensitivity. This underscores the need for rapid scale-up of viral assays for early infant diagnosis.

Stephen Gichuhi, Rose Bosire DM-N, Christine Gichuhi, Dalton Wamalwa, Maleche-Obimbo E, Farquhar C, Phelgona Otieno, Grace C. John-Stewart. "Risk factors for neonatal conjunctivitis in babies of HIV-1 infected mothers." Ophthalmic Epidemiol. 2009 ; 16(6): 337–345. doi:10.3109/09286580903144746. 2009. Abstractrisk_factors_for_neonatal_conjunctivitis_in_babies_of_hiv-1.pdf

Abstract
Purpose—To determine the prevalence and correlates of neonatal conjunctivitis in infants born
to human immunodeficiency virus type 1 (HIV-1) infected mothers.
Methods—This was a nested case-control study within a perinatal HIV-1 cohort. HIV-1
seropositive mothers were enrolled during pregnancy and mother-infant pairs followed after
delivery with assessment for neonatal conjunctivitis at 48 hours and up to 4 weeks after birth.
Genital infections (chlamydia, gonorrhea, syphilis, trichomonas, bacterial vaginosis, and candida)
were screened for at 32 weeks gestation. Mothers received treatment for genital infections
diagnosed during pregnancy and short-course zidovudine. Newborns did not receive ocular
prophylaxis at hospital deliveries. Multivariate logistic regression models were used to determine
cofactors for neonatal conjunctivitis overall and stratified for infant HIV-1 status.
Results—Four hundred and fifty-two infants were assessed and 101 (22.3%) had neonatal
conjunctivitis during the first month postpartum. In multivariate analyses using odds ratios (OR)
and confidence intervals (CI), neonatal conjunctivitis was associated with neonatal sepsis
(adjusted OR 21.95, 95% CI 1.76, 274.61), birth before arrival to hospital (adjusted OR 13.91,
95% CI 1.39, 138.78) and birth weight (median 3.4 versus 3.3 kilograms, p=0.016, OR 1.79, 95%
CI 1.01, 3.15). Infant HIV-1 infection was not associated with conjunctivitis.
Conclusions—Despite detection and treatment of genital infections during pregnancy, neonatal
conjunctivitis was frequently diagnosed in infants born to HIV-1 infected mothers suggesting a
need for increased vigilance and prophylaxis for conjunctivitis in these infants. Neonatal sepsis,
birth before arrival to hospital, and higher birthweight are factors that may predict higher risk of
neonatal conjunctivitis in this population.

2007
C. DRWAMALWADALTON, MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "Early response to highly active antiretroviral therapy in HIV-1-infected Kenyan children. J Acquir Immune Defic Syndr . 2007 Jul 1; 45 ( 3 ): 311-7 . PMID: 17356470 [PubMed - indexed for MEDLINE] Wamalwa DC, Farquhar C, Obimbo EM, Selig S, Mbori-Ngacha DA.". In: J Acquir Immune Defic Syndr . 2007 Jul 1; 45 ( 3 ): 311-7 . Kisipan, M.L.; 2007. Abstractearly_response_to_highly_active_antiretroviral_therapy.pdf

OBJECTIVES: To describe the early response to World Health Organization (WHO)-recommended nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line highly active antiretroviral therapy (HAART) in HIV-1-infected Kenyan children unexposed to nevirapine. DESIGN: Observational prospective cohort. METHODS: HIV-1 RNA level, CD4 lymphocyte count, weight for age z score, and height for age z score were measured before the initiation of HAART and every 3 to 6 months thereafter. Children received no nutritional supplements. RESULTS: Sixty-seven HIV-1-infected children were followed for a median of 9 months between August 2004 and November 2005. Forty-seven (70%) used zidovudine, lamivudine (3TC), and an NNRTI (nevirapine or efavirenz), whereas 25% used stavudine (d4T), 3TC, and an NNRTI. Nevirapine was used as the NNRTI by 46 (69%) children, and individual antiretroviral drug formulations were used by 63 (94%), with only 4 (6%) using a fixed-dose combination of d4T, 3TC, and nevirapine (Triomune; Cipla, Mumbai, India). In 52 children, the median height for age z score and weight for age z score rose from -2.54 to -2.17 (P<0.001) and from -2.30 to -1.67 (P=0.001), respectively, after 6 months of HAART. Hospitalization rates were significantly reduced after 6 months of HAART (17% vs. 58%; P<0.001). The median absolute CD4 count increased from 326 to 536 cells/microL (P<0.001), the median CD4 lymphocyte percentage rose from 5.8% before treatment to 15.4% (P<0.001), and the median viral load fell from 5.9 to 2.2 log10 copies/mL after 6 months of HAART (P<0.001). Among 43 infants, 47% and 67% achieved viral suppression to less than 100 copies/mL and 400 copies/mL, respectively, after 6 months of HAART. CONCLUSION: Good early clinical and virologic response to NNRTI-based HAART was observed in HIV-1-infected Kenyan children with advanced HIV-1 disease.
PMID: 17356470 [PubMed - indexed for MEDLINE]

C. DRWAMALWADALTON, MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "High uptake of postpartum hormonal contraception among HIV-1-seropositive women in Kenya. Sex Transm Dis . 2007 Jan; 34 ( 1 ): 25-9 . PMID: 16691159 [PubMed - indexed for MEDLINE] Balkus J, Bosire R, John-Stewart G, Mbori-Ngacha D, Schiff MA, Wamalwa D, G.". In: Sex Transm Dis . 2007 Jan; 34 ( 1 ): 25-9 . Kisipan, M.L.; 2007. Abstracthigh_uptake_of_postpartum_hormonal_contraception.pdf

Department of Epidemiology, University of Washington, Seattle, Washington 98104, USA. jbalkus@u.washington.edu
OBJECTIVES: The objectives of this study were to determine patterns of contraceptive utilization among sexually active HIV-1-seropositive women postpartum and to identify correlates of hormonal contraception uptake. GOAL: The goal of this study was to improve delivery of family planning services to HIV-1-infected women in resource-limited settings. STUDY DESIGN: HIV-1-infected pregnant women were followed prospectively in a perinatal HIV-1 transmission study. Participants were referred to local clinics for contraceptive counseling and management. RESULTS: Among 319 HIV-1-infected women, median time to sexual activity postpartum was 2 months and 231 (72%) women used hormonal contraception for at least 2 months during follow-up, initiating use at approximately 3 months postpartum (range, 1-11 months). Overall, 101 (44%) used DMPA, 71 (31%) oral contraception, and 59 (25%) switched methods during follow-up. Partner notification, infant mortality, and condom use were similar between those using and not using contraception. CONCLUSIONS: Using existing the healthcare infrastructure, it is possible to achieve high levels of postpartum hormonal contraceptive utilization among HIV-1-seropositive women.
PMID: 16691159 [PubMed - indexed for MEDLINE]

MBORI- PROFNGACHADOROTHYA, W. PROFNDUATIRUTH, ELIZABETH DROBIMBO. "HIV-1 Disease Progression in Breast-Feeding and Formula-Feeding Mothers: A Prospective 2-Year Comparison of T Cell Subsets, HIV-1 RNA Levels, and Mortality. Otieno PA, Brown ER, Mbori-Ngacha DA, Nduati RW, Farquhar C, Obimbo EM, Bosire RK, Emery S, Overba.". In: J Infect Dis. 2007 Jan 15;195(2):220-9. Epub 2006 Dec 13. Kisipan, M.L.; 2007. Abstract

Centre for Clinical Research, Kenya Medical Research Institute, University of Nairobi, Nairobi, Kenya. Background. There is conflicting evidence regarding the effects of breast-feeding on maternal mortality from human immunodeficiency virus type 1 (HIV-1) infection, and little is known about the effects of breast-feeding on markers of HIV-1 disease progression.Methods. HIV-1-seropositive women were enrolled during pregnancy and received short-course zidovudine. HIV-1 RNA levels and CD4 cell counts were determined at baseline and at months 1, 3, 6, 12, 18, and 24 postpartum and were compared between breast-feeding and formula-feeding mothers.Results. Of 296 women, 98 formula fed and 198 breast-fed. At baseline, formula-feeding women had a higher education level and prevalence of HIV-1-related illness than did breast-feeding women; however, the groups did not differ with respect to CD4 cell counts and HIV-1 RNA levels. Between months 1 and 24 postpartum, CD4 cell counts decreased 3.9 cells/ mu L/month (P<.001), HIV-1 RNA levels increased 0.005 log(10) copies/mL/month (P=.03), and body mass index (BMI) decreased 0.03 kg/m(2)/month (P<.001). The rate of CD4 cell count decline was higher in breast-feeding mothers (7.2 cells/ mu L/month) than in mothers who never breast-fed (4.0 cells/ mu L/month) (P=.01). BMI decreased more rapidly in breast-feeding women (P=.04), whereas HIV-1 RNA levels and mortality did not differ significantly between breast-feeding and formula-feeding women.Conclusions. Breast-feeding was associated with significant decreases in CD4 cell counts and BMI. HIV-1 RNA levels and mortality were not increased, suggesting a limited adverse impact of breast-feeding in mothers receiving extended care for HIV-1 infection.

C. DRWAMALWADALTON, MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "Morbidity among HIV-1-infected mothers in Kenya: prevalence and correlates of illness during 2-year postpartum follow-up. J Acquir Immune Defic Syndr . 2007 Oct 1; 46 ( 2 ): 208-15 . PMID: 17667334 [PubMed - indexed for MEDLINE] Walson JL, Brown ER, Otien.". In: J Acquir Immune Defic Syndr . 2007 Oct 1; 46 ( 2 ): 208-15 . Kisipan, M.L.; 2007. Abstractmorbidity_among_hiv-1-infected_mothers_in_kenya.pdf

Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya. walson@u.washington.edu
BACKGROUND: Much of the burden of morbidity affecting women of childbearing age in sub-Saharan Africa occurs in the context of HIV-1 infection. Understanding patterns of illness and determinants of disease in HIV-1-infected mothers may guide effective interventions to improve maternal health in this setting. METHODS: We describe the incidence and cofactors of comorbidities affecting peripartum and postpartum HIV-1-infected women in Kenya. Women were evaluated by clinical examination and standardized questionnaires during pregnancy and for up to 2 years after delivery. RESULTS: Five hundred thirty-five women were enrolled in the cohort (median CD4 count of 433 cells/mm) and accrued 7736 person-months of follow-up. During 1-year follow-up, the incidence of upper respiratory tract infections was 161 per 100 person-years, incidence of pneumonia was 33 per 100 person-years, incidence of tuberculosis (TB) was 11 per 100 person-years, and incidence of diarrhea was 63 per 100 person-years. Immunosuppression and HIV-1 RNA levels were predictive for pneumonia, oral thrush, and TB but not for diarrhea; CD4 counts <200 cells/mm(3) were associated with pneumonia (relative risk [RR] = 2.87, 95% confidence interval [CI]: 1.71 to 4.83), TB (RR = 7.14, 95% CI: 2.93 to 17.40) and thrush. The risk of diarrhea was significantly associated with crowding (RR = 1.86, 95% CI: 1.19 to 2.92) and breast-feeding (RR = 1.71, 95% CI: 1.19 to 2.44). Less than 10% of women reported hospitalization during 2-year follow-up; mortality risk in the cohort was 1.9% and 4.8% for 1 and 2 years, respectively. CONCLUSIONS: Mothers with HIV-1, although generally healthy, have substantial morbidity as a result of common infections, some of which are predicted by immune status or by socioeconomic factors. Enhanced attention to maternal health is increasingly important as HIV-1-infected mothers transition from programs targeting the prevention of mother-to-child transmission to HIV care clinics.
PMID: 17667334 [PubMed - indexed for MEDLINE]

2005
MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "Longitudinal assessment of human immunodeficiency virus type 1 (HIV-1)-specific gamma interferon responses during the first year of life in HIV-1-infected infants. J Virol . 2005 Jul; 79 ( 13 ): 8121-30 . PMID: 15956557 [PubMed - indexed for MEDLINE] Lohm.". In: J Virol . 2005 Jul; 79 ( 13 ): 8121-30 . Kisipan, M.L.; 2005. Abstract
Department of Paediatrics, University of Nairobi, Kenya. bllohman@iconnect.co.ke Human immunodeficiency virus type 1 (HIV-1) infection results in different patterns of viral replication in pediatric compared to adult populations. The role of early HIV-1-specific responses in viral control has not been well defined, because most studies of HIV-1-infected infants have been retrospective or cross-sectional. We evaluated the association between HIV-1-specific gamma interferon (IFN-gamma) release from the cells of infants of 1 to 3 months of age and peak viral loads and mortality in the first year of life among 61 Kenyan HIV-1-infected infants. At 1 month, responses were detected in 7/12 (58%) and 6/21 (29%) of infants infected in utero and peripartum, respectively (P = 0.09), and in approximately 50% of infants thereafter. Peaks of HIV-specific spot-forming units (SFU) increased significantly with age in all infants, from 251/10(6) peripheral blood mononuclear cells (PBMC) at 1 month of age to 501/10(6) PBMC at 12 months of age (P = 0.03), although when limited to infants who survived to 1 year, the increase in peak HIV-specific SFU was no longer significant (P = 0.18). Over the first year of life, infants with IFN-gamma responses at 1 month had peak plasma viral loads, rates of decline of viral load, and mortality risk similar to those of infants who lacked responses at 1 month. The strength and breadth of IFN-gamma responses at 1 month were not significantly associated with viral containment or mortality. These results suggest that, in contrast to HIV-1-infected adults, in whom strong cytotoxic T lymphocyte responses in primary infection are associated with reductions in viremia, HIV-1-infected neonates generate HIV-1-specific CD8+-T-cell responses early in life that are not clearly associated with improved clinical outcomes. PMID: 15956557 [PubMed - indexed for MEDLINE] PMCID: PMC1143755
C. DRWAMALWADALTON, MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "Predictors of mortality in HIV-1 exposed uninfected post-neonatal infants at the Kenyatta National Hospital, Nairobi. East Afr Med J . 2005 Sep; 82 ( 9 ): 447-51 . PMID: 16619717 [PubMed - indexed for MEDLINE] Gichuhi C, Obimbo E, Mbori-Ngacha D, Mwatha A.". In: East Afr Med J . 2005 Sep; 82 ( 9 ): 447-51 . Kisipan, M.L.; 2005. Abstract
{ Department of Clinical Pharmacology and Therapeutics, College of Health Sciences, University of Nairobi, P.O. Box 19676, Nairobi, Kenya. 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
2004
MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "Predictors of early mortality in a cohort of human immunodeficiency virus type 1-infected african children. Pediatr Infect Dis J . 2004 Jun; 23 ( 6 ): 536-43 . PMID: 15194835 [PubMed - indexed for MEDLINE] Obimbo EM, Mbori-Ngacha DA, Ochieng JO, Richardso.". In: Pediatr Infect Dis J . 2004 Jun; 23 ( 6 ): 536-43 . Kisipan, M.L.; 2004. Abstractpredictors_of_early_mortality_in_a_cohort_of_human.pdf

{
Department of Pediatrics, University of Nairobi, Nairobi, Kenya.
BACKGROUND: Pediatric human immunodeficiency virus type 1 (HIV-1) infection follows a bimodal clinical course with rapid progression in 10-45% of children before the age of 2 years and slower progression in the remainder. A prospective observational study was undertaken to determine predictors of mortality in HIV-1-infected African infants during the first 2 years of life. METHODS: Infants in a perinatal cohort identified to be HIV-1-infected by DNA PCR were followed monthly to 1 year, then quarterly to 2 years or death. RESULTS: Among 62 HIV-1-infected infants, infection occurred by the age of 1 month in 56 (90%) infants, and 32 (52%) died at median age of 6.2 months. All infant deaths were caused by infectious diseases, most frequently pneumonia (75%) and diarrhea (41%). Univariate predictors of infant mortality included maternal CD4 count <200 cells/microl [hazard ratio (HR), 3.4; P = 0.008], maternal anemia (HR = 3.7; P = 0.005), delivery complications (HR = 2.7; P = 0.01), low birth weight (HR = 4.1; P = 0.001), weight, length and head circumference

FLORENCE DRMURILA, MASIBO PROFWAFULAEZEKIEL, ELIZABETH DROBIMBO. "Bacteraemia, urinary tract infection and malaria in hospitalised febrile children in Nairobi: is there an association? East Afr Med J . 2004 Jan; 81 ( 1 ): 47-51 . PMID: 15080516 [PubMed - indexed for MEDLINE] Okwara FN, Obimbo EM, Wafula EM, Murila FV.". In: East Afr Med J . 2004 Jan; 81 ( 1 ): 47-51 . Kisipan, M.L.; 2004. Abstract
Department of Paediatrics and Child Health, College of Health Sciences, University of Nairobi, P.O. Box 19676, Nairobi, Kenya. BACKGROUND: There is laboratory evidence of altered immune function in children with malaria. Bacterial infections have been documented to complicate severe forms of malaria. However, it remains unclear whether such infections are attributable to the malaria, other risk factors, or are coincidental. OBJECTIVE: To determine the prevalence of bacteraemia and urinary tract infections (UTI) in febrile hospitalised children with and without malaria. DESIGN: A cross-sectional survey. SETTING: General paediatric wards, Kenyatta National Hospital, Nairobi. SUBJECTS: Children aged between three months and 12 years admitted with an acute febrile illness, with no obvious focus of bacterial infection. MATERIALS AND METHODS: Using a standardised questionnaire, information on socio-demography, symptomatology, and nutritional status was obtained. Malaria slides, blood and urine cultures were performed on each child. RESULTS: Malaria parasitaemia was present in 158 (60%) of 264 children presenting with acute febrile illness with no obvious focus of bacterial infection. Bacteria were isolated from blood and/or urine of 62 (23%) of all enrolled children. Bacteraemia was prevalent among 11.4% of 158 children with malaria and among 13.2% of 106 without malaria. Gram-positive organisms comprised 28.1% of blood isolates, gram-negative 62.5%, and atypical bacteria 9.4%. UTI was prevalent among 13.3% of 158 children with malaria and 16.0% of 106 children without malaria. Gram-positive organisms comprised 18.4%, gram-negative 78.9%, and atypical bacteria 2.6% of the urine isolates. Presence of malaria parasitaemia was not associated with an increased risk of bacteraemia (OR 0.9, 95% CI [0.4-0.7], or UTI (OR 0.8 95% CI [0.4-1.6] in this study population. CONCLUSION: Among children hospitalised in Nairobi with fever and no obvious bacterial infective focus, there should be a high index of suspicion for malaria, followed by bacteraemia and UTI. Malaria parasitaemia does not appear to be associated with increased risk of bacterial co-infection. PMID: 15080516 [PubMed - indexed for MEDLINE]
MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "Human leukocyte antigen (HLA) B*18 and protection against mother-to-child HIV type 1 transmission. AIDS Res Hum Retroviruses . 2004 Jul; 20 ( 7 ): 692-7 . PMID: 15307911 [PubMed - indexed for MEDLINE] Farquhar C, Rowland-Jones S, Mbori-Ngacha D, Redman M,.". In: AIDS Res Hum Retroviruses . 2004 Jul; 20 ( 7 ): 692-7 . Kisipan, M.L.; 2004. Abstract
Department of Medicine, University of Washington, Seattle, Washington 98104, USA. cfarq@u.washington.edu Human leukocyte antigen (HLA) molecules regulate the cellular immune system and may be determinants of infant susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. Molecular HLA typing for class I alleles was performed on infants followed in a Kenyan perinatal cohort. Early HIV-1 infection status was defined as infection occurring at birth or month 1, while late infection via breast milk was defined as first detection of HIV-1 after 1 month of age. Likelihood ratio tests based on a proportional hazards model adjusting for maternal CD4 T cell count and HIV-1 viral load at 32 weeks of gestation were used to test associations between infant allelic variation and incident HIV-1 infection. Among 433 infants, 76 (18%) were HIV-1 infected during 12 months of follow-up. HLA B*18 was associated with a significantly lower risk of early HIV-1 transmission [relative risk (RR) = 0.26; 95% confidence interval (CI) 0.04-0.82], and none of the 24 breastfeeding infants expressing HLA B*18 who were uninfected at month 1 acquired HIV-1 late via breast milk. We observed a trend toward increased early HIV-1 acquisition for infants presenting HLA A*29 (RR = 2.0; 95% CI 1.0-3.8) and increased late HIV-1 acquisition via breast milk for both Cw*07 and Cw*08 (RR = 4.0; 95% CI 1.0-17.8 and RR = 7.2; 95% CI 1.2-37.3, respectively). HLA B*18 may protect breast-feeding infants against both early and late HIV-1 acquisition, a finding that could have implications for the design and monitoring of HIV-1 vaccines targeting cellular immune responses against HIV-1. PMID: 15307911 [PubMed - indexed for MEDLINE]
MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "Obimbo EM, Mbori-Ngacha DA, Ochieng JO, Richard BA, Otieno PA, Bosire R, Farquhar C, Overbaugh J, John-Stewart GC. Predictors of Early Mortality in a Cohort of Human Immunodeficiency Virus Type-1 .". In: Pediatr Infect Dis J. 2004 Jun;23(6)536-543. East Afr Med J. 2005 Sep;82(9):447-51. Kisipan, M.L.; 2004. Abstract
{ Department of Clinical Pharmacology and Therapeutics, College of Health Sciences, University of Nairobi, P.O. Box 19676, Nairobi, Kenya. 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
2003
MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "Lohman B, Slyker J, Mbori-Ngacha D, Bosire R, Farquhar C, Obimbo E, Otieno P, Nduati R, Rowland-Jones S, John-Stewart G. Prevalence and Magnitude of HIV-1-specific Lymphocyte Responses in Breast Milk from HIV-1 Seropositive Women. J Infect Dis. 2003:188:1.". In: J Infect Dis. 2003:188:1666-1674. Kisipan, M.L.; 2003. Abstract
Department of Medical Microbiology, University of Nairobi, Kenya. Human immunodeficiency virus (HIV) type 1-specific cell-mediated immunity of breast milk may influence the likelihood of mother-to-child transmission of HIV-1 via breast-feeding. In breast-milk specimens collected during the first month postpartum from HIV-1-seropositive women in Nairobi, HIV-1 gag-specific cellular responses were detected in 17 (47%) of 36, and env-specific cellular responses were present in 20 (40%) of 50. Peripheral blood lymphocyte responses against either gag or env were detected in 35 (66%) of the 53 subjects, 18 (51%) of whom had positive gag or env responses in their breast milk. In paired analyses of blood and breast milk, the mean magnitude of responses to env or gag stimulation in breast milk was significantly higher than that in blood and remained higher in breast milk after normalization of responses according to CD8+ lymphocyte count. These results suggest that CD8+ lymphocytes present in breast milk have the capacity to recognize HIV-1-infected cells and may be selectively transported to breast milk to reduce either viral replication or transmission in breast milk.
MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "Lohman B, Slyker J, Mbori-Ngacha D, Bosire R, Farquhar C, Obimbo E., Otieno P, Nduati R, Rowland-Jones S, John-Stewart G. Prevalence and Magnitude of HIV-1-specific Lymphocyte Responses in Breast Milk from HIV-1 Seropositive Women. J. Infect Dis. Dec 2003.". In: J. Infect Dis. Dec 2003; 1888 (11) 1999-74. Kisipan, M.L.; 2003. Abstract
Department of Medical Microbiology, University of Nairobi, Kenya. Human immunodeficiency virus (HIV) type 1-specific cell-mediated immunity of breast milk may influence the likelihood of mother-to-child transmission of HIV-1 via breast-feeding. In breast-milk specimens collected during the first month postpartum from HIV-1-seropositive women in Nairobi, HIV-1 gag-specific cellular responses were detected in 17 (47%) of 36, and env-specific cellular responses were present in 20 (40%) of 50. Peripheral blood lymphocyte responses against either gag or env were detected in 35 (66%) of the 53 subjects, 18 (51%) of whom had positive gag or env responses in their breast milk. In paired analyses of blood and breast milk, the mean magnitude of responses to env or gag stimulation in breast milk was significantly higher than that in blood and remained higher in breast milk after normalization of responses according to CD8+ lymphocyte count. These results suggest that CD8+ lymphocytes present in breast milk have the capacity to recognize HIV-1-infected cells and may be selectively transported to breast milk to reduce either viral replication or transmission in breast milk.
MBORI- PROFNGACHADOROTHYA, ELIZABETH DROBIMBO. "Prevalence and Magnitude of Human Immunodeficiency Virus (HIV) Type 1-Specific Lymphocyte Responses in Breast Milk from HIV-1-Seropositive Women. J Infect Dis. 2003 Dec 1;188(11):1666-74. Lohman BL, Slyker J,Mbori-Ngacha D, Bosire R, Farquhar C, Obimbo E,.". In: J Infect Dis. 2003 Dec 1;188(11):1666-74. Kisipan, M.L.; 2003. Abstract
Department of Medicine, University of Washington, Seattle, Washington 98104, USA. cfarq@u.washington.edu Human leukocyte antigen (HLA) molecules regulate the cellular immune system and may be determinants of infant susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. Molecular HLA typing for class I alleles was performed on infants followed in a Kenyan perinatal cohort. Early HIV-1 infection status was defined as infection occurring at birth or month 1, while late infection via breast milk was defined as first detection of HIV-1 after 1 month of age. Likelihood ratio tests based on a proportional hazards model adjusting for maternal CD4 T cell count and HIV-1 viral load at 32 weeks of gestation were used to test associations between infant allelic variation and incident HIV-1 infection. Among 433 infants, 76 (18%) were HIV-1 infected during 12 months of follow-up. HLA B*18 was associated with a significantly lower risk of early HIV-1 transmission [relative risk (RR) = 0.26; 95% confidence interval (CI) 0.04-0.82], and none of the 24 breastfeeding infants expressing HLA B*18 who were uninfected at month 1 acquired HIV-1 late via breast milk. We observed a trend toward increased early HIV-1 acquisition for infants presenting HLA A*29 (RR = 2.0; 95% CI 1.0-3.8) and increased late HIV-1 acquisition via breast milk for both Cw*07 and Cw*08 (RR = 4.0; 95% CI 1.0-17.8 and RR = 7.2; 95% CI 1.2-37.3, respectively). HLA B*18 may protect breast-feeding infants against both early and late HIV-1 acquisition, a finding that could have implications for the design and monitoring of HIV-1 vaccines targeting cellular immune responses against HIV-1. PMID: 15307911 [PubMed - indexed for MEDLINE]
ELIZABETH DROBIMBO. "Primary health care, selective or comprehensive, which way to go? East Afr Med J . 2003 Jan; 80 ( 1 ): 7-10 . Review. PMID: 12755235 [PubMed - indexed for MEDLINE] Obimbo EM.". In: East Afr Med J . 2003 Jan; 80 ( 1 ): 7-10 . Review. PMID: 12755235 [PubMed - indexed for MEDLINE]. Kisipan, M.L.; 2003. Abstract

Department of Paediatrics and Child Health, College of Health Sciences, University of Nairobi, P.O. Box 19676, Nairobi, Kenya. OBJECTIVE: To critically review the advantages and disadvantages of selective versus comprehensive Primary Health Care (PHC) approaches as a strategy towards improving health in the developing world. DATA SOURCES: Review of literature on PHC. DATA SELECTION: Relevant papers from western and developing world literature. DATA EXTRACTION: Search of Pub-Med, WHO/UNICEF reports, and relevant publications on PHC. DATA SYNTHESIS: Examination of principles behind PHC and practical experiences in PHC in the developing world. CONCLUSIONS: Selective PHC programs have improved specific aspects of health, frequently at the expense of other health sectors, but fail to address an individual's health in holistic manner, or the health infrastructure of countries. Selective PHC programs tend to focus only on a small subset of the community. Comprehensive PHC is expensive to implement, however addresses health of individuals more holistically, addresses both preventive and curative health care, and promotes health infrastructure development and community involvement, thereby providing more sustainable improvement of health in the whole community. PMID: 12755235 [PubMed - indexed for MEDLINE]

2001
ELIZABETH DROBIMBO. "Emerging issues in measles. East Afr Med J . 2001 Jan; 78 ( 1 ): 1-3 . No abstract available. PMID: 11320756 [PubMed - indexed for MEDLINE] Obimbo EM.". In: East Afr Med J . 2001 Jan; 78 ( 1 ): 1-3 . Kisipan, M.L.; 2001. Abstract
No abstract available.
1999
N PROFMUSOKERACHEL, ELIZABETH DROBIMBO, N PROFWEREFREDRICK. "Obimbo E, Musoke RN, Were F. Knowledge, attitudes and practices of mothers and knowledge of health workers regarding care of the newborn umbilical cord. E. Afr Med J, 1999: 76 (8); 425-429.". In: East Afr Med J. 1999 Aug;76(8):425-9. Kisipan, M.L.; 1999. Abstract
Department of Paediatrics and Child Health, College of Health Sciences, University of Nairobi. OBJECTIVE: To determine the knowledge, attitudes and practices (KAP) of mothers and the knowledge of health workers regarding care of the newborn umbilical cord. DESIGN: Cross-sectional survey. SUBJECTS: Mothers with infants less than three months of age attending well child clinics and health workers (HW) in the clinics, maternity and newborn units of public health, facilities serving an urban slum area in Nairobi, Kenya. RESULTS: Of the 307 mothers interviewed, 91% and 28% of mothers knew of the need for hygiene whilst cutting and tying the cord, respectively. Regarding postnatal cord care, 40% had good knowledge and 66% good practice. Fifty-one percent of mothers knew and 54% practised postnatal cord care for the appropriate duration of time. Seventy-nine percent of mothers were afraid of handling an unhealed cord. After multivariate analysis, the following variables showed significant independent association with good maternal KAP; increased level of education (OR 2.3, p < 0.001), living in middle class areas rather than slums (OR 1.5, p < 0.03), increased maternal age (OR 1.8, p < 0.001), acquisition of knowledge from a HW rather than from other sources (OR 1.5, p < 0.001), and living in stone/brick houses rather than mud houses (p = 0.01). Fifty per cent of HW had correct knowledge on type of postnatal cord care, and 79% had correct knowledge on duration required for the same. The knowledge of 50% on type of care was incorrect by international standards, but was in keeping with Nursing Council of Kenya teaching. CONCLUSION: Mothers had good knowledge on the need for hygiene when cutting the cord, had poor knowledge and practice in other aspects of cord care, and were afraid of handling the cord. Poor KAP was associated with young, poor mothers of low education, who had acquired their knowledge from sources other than HW. The knowledge of a large proportion of HW was incorrect and outdated. We recommend that health education on cord care be given at all levels of contact with mothers and that knowledge of all primary HW on cord care be updated. PIP: Using a cross-sectional survey, this study investigated the knowledge, attitudes, and practices (KAP) of mothers and the knowledge of health workers regarding care of the umbilical cord. The study interviewed a total of 307 mothers with infants less than 3 months old and 64 health workers (HWs) in an urban slum area in Nairobi, Kenya. The results showed that 91% and 28% of mothers knew of the need for hygiene while cutting and tying the cord, respectively. As to postnatal cord care, 40% had good knowledge and 66% had good practice. However, 79% of mothers were afraid of handling an unhealed cord. Results of multivariate analysis showed that the following variables had significant independent association with good maternal KAP: increased level of education, living in middle class areas, increased maternal age, and acquisition of knowledge from HWs rather than from other sources. 50% of HWs had correct knowledge on type of postnatal cord care, but the knowledge of 50% on type of care was incorrect by international standards. Based on the findings, it was recommended that good health and cord care practices be taught at all levels of contact with mothers and that knowledge of all primary HWs on cord care be updated.
1998
Marty M, Blotman F, Avouac B, Rozenberg S, Valat JP. "Validation of the French version of the Dallas Pain Questionnaire in chronic low back pain patients." Rev Rhum Engl Ed. 1998;65(2):126-34. Abstract

To translate and to validate the metrological properties of the Dallas Pain Questionnaire, an instrument designed to evaluate the impact of low back pain on four aspects of patients' lives: daily activities, work and leisure activities, anxiety/depression and social interest.

1987
Serra AJ, McNicholas KW, Olivier HF, Boe SL, Lemole GM. "The choice of anticoagulation in pediatric patients with the St. Jude Medical valve prostheses." J Cardiovasc Surg (Torino). 1987;28(5):588-91. Abstract

Between February 1982 and January 1984 27 St. Jude Medical cardiac valve prostheses were implanted in 24 children ranging in age from 5 to 20 years (mean 12.38 years). There were 10 isolated aortic valve replacements, 14 isolated mitral valve replacements and one triple valve replacement (aortic, mitral and tricuspid). There was one operative and four late deaths. All patients were maintained on Aspirin and Dipyridamole from the early postoperative period. There were six documented thromboembolic events occurring in five patients. There were 0.68 thromboembolic events per patient year in the aortic valve group and 0.19 events in the mitral valve group. Because of the significant incidence of thromboembolic events in our patients, we now recommend universal anticoagulation with Coumadin in all pediatric age patients in whom the St. Jude Medical prosthesis is implanted.

Tung CS, Chu KM, Tseng CJ, Yin TH. "Adenosine in hemorrhagic shock: possible role in attenuating sympathetic activation." Life Sci.. 1987;41(11):1375-82. Abstract

Changes in plasma purine nucleoside level, autonomic activity and hemodynamic reactions were studied in pentobarbital anesthetized rabbits during hemorrhagic shock. Shock was elicited by bleeding the animals to a mean blood pressure of 40 mmHg and maintained until 60% of the maximum bleeding volume in the reservoir had been taken up spontaneously. The remaining shed blood was reinfused thereafter. Norepinephrine (NE), epinephrine (E), adenosine (AD) and uric acid were measured by HPLC with electrochemical detection, fluorometry or UV absorbance. The results showed hemorrhagic shock caused a significant rise in plasma NE, E, AD, and uric acid levels, but the magnitudes and time profiles were different among them. Plasma NE and E increased during the shock compensatory period then declined in the decompensation period whereas adenosine and its metabolite uric acid were elevated persistently during both periods. It is concluded that a balance between autonomic activity and tissue metabolism is important in the maintenance of hemodynamics during shock.

Shibata S. "Unique vasocontraction of okadaic acid isolated from black sponge, independent of extracellular Ca2+." Blood Vessels. 1987;24(3):104-7. Abstract

Okadaic acid (OA) isolated from black sponge (Halichondria) caused tonic contractions of human umbilical arteries and rabbit aorta both in the presence and absence of Ca2+. This tonic contraction was not affected by Ca2+ chelator, Ca2+ entry blockers and La3+. In addition, the antagonists of alpha-adrenoceptors, histamine, serotonin and ACh receptors had no effect on the OA-induced contraction. High K, ouabain and indomethacin failed to inhibit the response to OA. However, the combination of anaerobic conditions and absence of glucose abolished the response to OA. OA had no effect on the myosin B ATPase and saponin-treated skinned fibers of rabbit aorta. The contractile action of OA may not also be related to calmodulin-related PDE and mitochondrial respiration. In conclusion, although the precise mode of action is not evident at the present time, OA, in its unique pharmacological action--that of producing sustained contraction independent of extracellular Ca2+--may alter the handling of Ca2+ to intracellular store sites.

1978
Simanovskaia VK, Kadishaite DL, Lisok TP, Siminina AA, Goluveb DB. "[Characterization of biological properties and glycopeptide composition of influenza virus type A grown in different cell systems]." Virologie. 1978;29(4):275-81.
Rodineau P. "[Elementary respiratory care in the postoperative period]." Anesth Analg (Paris). 1978;35(4):677-84.
1976
Stamm O, Latscha U, Janecek P, Campana A. "Development of a special electrode for continuous subcutaneous pH measurement in the infant scalp." Am. J. Obstet. Gynecol.. 1976;124(2):193-5. Abstract

Using a combined special glass electrode it is possible to monitor pH ratios and pH variation in the subcutaneous tissue of the infant scalp continuously. Tests on a normal sample of newborn babies immediately after birth showed a significant correlation between tissue pH and capillary blood pH, with the trend of pH variation being broadly similar in both measurement media.

Bland RD, Clarke TL, Harden LB. "Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial." Am. J. Obstet. Gynecol.. 1976;124(3):263-7. Abstract

We conducted a controlled, prospective trial to evaluate the effectiveness of rapidly infusing sodium bicarbonate (NaHCO3) and salt-poor albumin into high-risk, premature infants in the first 2 hours of life. Fifty-three infants, randomized into one of four treatment groups, received 8 ml. per kilogram of a solution containing either (A) glucose in water, (B) salt-poor albumin, (C) NaHCO3, or (D) a combination of albumin and NaHCO3. After the initial infusion, the babies received no colloid or alkali solutions until 4 hours of age. We managed them supportively with warmth, appropriate oxygen administration, isotonic fluid infusion, and close monitoring. Among the infants who received alkali, 14 of 26 acquired the respiratory distress syndrome (RDS), 11 died, and four had intracranial hemorrhage. Among babies who received no alkali, RDS occurred in 11 of 27, 5 died, and none had intracranial hemorrhage. These results do not support the common practice of rapidly infusing NaHCO3 into high-risk, premature infants, and they suggest that the early management of such infants needs renewed critical evaluation.

1975
Bhagwat VM, Ramachandran BV. "Malathion A and B esterases of mouse liver-I." Biochem. Pharmacol.. 1975;24(18):1713-7.
Schmoldt A, Benthe HF, Haberland G. "Digitoxin metabolism by rat liver microsomes." Biochem. Pharmacol.. 1975;24(17):1639-41.
Coscia L, Causa P, Giuliani E, Nunziata A. "Pharmacological properties of new neuroleptic compounds." Arzneimittelforschung. 1975;25(9):1436-42. Abstract

RMI 61 140, RMI 61 144 and RMI 61 280 are newly synthetized N-[8-R-dibenzo(b,f)oxepin-10-yl]-N'-methyl-piperazine-maleates which show interesting psychopharmacologic effects. This work contains the results of a study performed with these three compounds, in order to demonstrate their neuropsycholeptic activity in comparison with chloropromazine (CPZ) and chlordiazepoxide (CPD). The inhibition of motility observed in mice shows that the compounds reduce the normal spontaneous motility as well as the muscle tone. The central-depressant activity is evidenced by increased barbiturate-induced sleep and a remarkable eyelid ptosis can also be observed. Our compounds do not show any activity on electroshock just as do CPZ and CPD. As to the antipsychotic outline, our compounds show strong reduction of lethality due to amphetamine in grouped mice and a strong antiapomorphine activity. They show also an antiaggressive effect and an inhibitory activity on avoidance behaviour much stronger than CPZ. We have also found extrapyramidal effects, as catalepsy, common to many tranquillizers of the kind of the standards used by us. As for vegetative phenomena, the compounds show hypotensive dose related action ranging from moderate to strong, probably due to an a-receptor inhibition. Adrenolytic activity against lethal doses of adrenaline, antiserotonin and antihistaminic effects, as well as other actions (hypothermia, analgesia, etc.) confirm that RMI 61 140, RMI 61 144 and RMI 61 280 are endowed with pharmacologic properties similar and more potent than those of CPZ. Studies on the metabolism of brain catecholamines show that they are similar to CPZ, although with less effect on dopamine level.

Wiesmann UN, DiDonato S, Herschkowitz NN. "Effect of chloroquine on cultured fibroblasts: release of lysosomal hydrolases and inhibition of their uptake." Biochem. Biophys. Res. Commun.. 1975;66(4):1338-43.
Smith RJ, Bryant RG. "Metal substitutions incarbonic anhydrase: a halide ion probe study." Biochem. Biophys. Res. Commun.. 1975;66(4):1281-6.
Chow YW, Pietranico R, Mukerji A. "Studies of oxygen binding energy to hemoglobin molecule." Biochem. Biophys. Res. Commun.. 1975;66(4):1424-31.
Barthel W, Markwardt F. "Aggregation of blood platelets by adrenaline and its uptake." Biochem. Pharmacol.. 1975;24(20):1903-4.
Imamura K. "[Studies on the energy for sperm motility (author's transl)]." Nihon Funin Gakkai Zasshi. 1975;20(4):6-13.
Kumar R, Tao M. "Multiple forms of casein kinase from rabbit erythrocytes." Biochim. Biophys. Acta. 1975;410(1):87-98. Abstract

Two rabbit erythrocyte casein kinases, GTP:casein kinase I and GTP:casein kinase II, have been purified 29 000- and 47 000-fold, respectively. Studies employing sucrose density gradient centrifugation indicate that kinase I has a molecular weight of about 9.5 - 10(5) (25 S) and kinase II about 1.4 - 10(6) (32 S). These enzymes can utilize either ATP or GTP as the phosphoryl donor. Among various protein substrates examined, these kinases catalyze the phosphorylation of casein greater than 50% dephosphorylated phosvitin congruent to 50% dephosphorylated casein greater than phosvitin. Histones, protamine and bovine serum albumin are poor phosphoryl acceptors. Kinetic data indicate that both enzymes are inhibited by high casein substrate concentrations which may be partially relieved by NaCl. Both phosphotransferases require Mg(2+) for activity and are optimally active at pH 9.0. The enzymes have apparent Km values of 2.5 - 10(-5) M for GTP, 2 - 10(-5) M for ATP, and 0.4--0.6 mg/ml for casein. The incorporation of the terminal phosphate of GTP into casein as catalyzed by these enzymes is inhibited to varying degrees by ATP, ITP, ADP, and GDP but not by UTP, CTP, GMP, adenosine 3':5'-cyclic monophosphate, and guanosine 3':5'-cyclic monophosphate. In addition, NaF and 2,3-diphosphoglyceric acid are also found to inhibit the activity of both kinases. The effect of 2,3-diphosphoglycerate is interesting and suggests that this metabolite may regulate the activity of the casein kinases in the red blood cells.

Moroff G, Brandt KG. "Yeast glutathione reductase. Studies of the kinetics and stability of the enzyme as a function of pH and salt concentration." Biochim. Biophys. Acta. 1975;410(1):21-31. Abstract

1. The pH dependencies of the apparent Michaelis constant for oxidized glutathione and the apparent turnover number of yeast glutathione reductase (EC 1.6.4.2) have been determined at a fixed concentration of 0.1 mM NADPH in the range pH 4.5--8.0. Between pH 5.5 and 7.6, both of these parameters are relatively constant. The principal effect of low pH on the kinetics of the enzyme-catalyzed reaction is the observation of a pH-dependent substrate inhibition by oxidized glutathione at pH less than or equal 7, which is shown to correlate with the binding of oxidized glutathione to the oxidized form of the enzyme. 2. The catalytic activity of yeast glutathione reductase at pH 5.5 is affected by the sodium acetate buffer concentration. The stability of the oxidized and reduced forms of the enzyme at pH 5.5 and 25 degrees C in the absence of bovine serum albumin was studied as a function of sodium acetate concentration. The results show that activation of the catalytic activity of the enzyme at low sodium acetate concentration correlates with an effect of sodium acetate on a reduced form of the enzyme. In contrast, inhibition of the catalytic activity of the enzyme at high sodium acetate concentration correlates with an effect of sodium acetate on the oxidized form of the enzyme.

Makar AB, McMartin KE, Palese M, Tephly TR. "Formate assay in body fluids: application in methanol poisoning." Biochem Med. 1975;13(2):117-26.
Alekseeva IG, Lapina GP, Tulovskaia ZD, Izmaĭlova VN. "[Structure formation in interphase adsorption layers of lysozyme at liquid boundaries]." Biofizika. 1975;20(4):566-9. Abstract

In connection with the modelling of biomembranes regularities of the formation and development of interphase adsorption layers of lysozyme at liquid borders under different conditions and depending on the nature of carbohydrate phase were investigated by the determination of mechanical characteristics of such layers. The investigations carried out showed that the most solid layers appeared under the conditions which assured the formation of the maximum number of intermolecular bonds (which in a common case is performed with maximum disorderlinesss of the macromolecules which get at the interphase).

Robinson JV, James AL. "Some observations on the effects produced in white mice following the injection of certain suspensions of corroding bacilli." Br J Exp Pathol. 1975;56(1):14-6. Abstract

Strictly anaerobic and facultatively anaerobic strains of "corroding bacilli" failed to produce any pathological symptoms when injected into white mice and no viable organisms could be recovered after 7 days. However, when these same strains were coupled with certain other living bacteria or certain sterile bacterial extracts, lesions developed from which corroding bacilli could be isolated even after 21 days.

Ward CW. "Aminopeptidases in webbing clothes moth larvae. Properties and specificities of the enzymes of intermediate electrophoretic mobility." Biochim. Biophys. Acta. 1975;410(2):361-9. Abstract

The major group of aminopeptidases (EC 3.4.11.-) of intermediate electrophoretic mobility, from Tineola bisselliella larvae, hav been fractionated into six bands by preparative polyacrylamide gel electrophoresis and the properties of these fractions investigated. They resemble each other in their pH optima of 8.2, their molecular weight of 240 000, their responses to various active site inhibitors and metal cations, and their specificities towards seventeen L-amino-acyl-beta-naphthylamide substrates. The derivatives of methionine, leucine, alanine, lysine, arginine and glutamic acid were those most rapidly hydrolysed. They appear to be true aminopeptidases hydrolysing amino acid amides, dipeptides and oligopeptides from the N-terminal end.

Fleet GH, Phaff HJ. "Glucanases in Schizosaccharomyces. Isolation and properties of an exo-beta-glucanase from the cell extracts and culture fluid of Schizosaccharomyces japonicus var. versatilis." Biochim. Biophys. Acta. 1975;410(2):318-32. Abstract

(11 Cell extracts and extracellular culture fluids of species of the yeast genus Schizosaccharomyces exhibited exo-beta-(1 leads to 3)- and exo-beta-(1 leads to 6)-glucanase (EC 3.2.1.-) activities. (2) Using a combination of Sephadex G-100 and DEAE-cellulose chromatography, the exo-beta-(1 leads to 3)-glucanases from the cell extracts and culture fluid of Schizosaccharomyces japonicus var. versatilis were purified extensively. The enzymes from either location exhibited similar purification and other properties. (3) The purified enzymes hydrolysed the beta-(1 leads to 6)-glucosidic linkage in addition to the beta-(1 leads to 3) linkage. Heat denaturation, inhibition and electrophoretic studies indicated that both hydrolytic activities were properties of a single protein. Laminarin and pustulan hydrolysis followed Michaelis-Menten kinetics. The Km and V for laminarin hydrolysis were 6.25 mg/ml and 350 mumol of glucose released/min/mg protein, and for pustulan they were 166 mg/ml and 52 mumol of glucose released/min/mg protein. (4) The exo-beta-glucanase was assigned a molecular weight of 43 000. (5) the purified enzyme failed to hydrolyse isolated cell walls from either baker's yeast or Schizosaccharomyces pombe or to induce protoplast formation from intact cells of S. japonicus var. versatilis or Saccharomyces cerevisiae.

Van Gorkom HJ, Pulles MP, Wessels JS. "Light-induced changes of absorbance and electron spin resonance in small photosystem II particles." Biochim. Biophys. Acta. 1975;408(3):331-9. Abstract

Photosystem II reaction center components have been studied in small system II particles prepared with digitonin. Upon illumination the reduction of the primary acceptor was indicated by absorbance changes due to the reduction of a plastoquinone to the semiquinone anion and by a small blue shifts of absorption bands near 545 nm (C550) and 685 nm. The semiquinone to chlorophyll ratio was between 1/20 and 1/70 in various preparations. The terminal electron donor in this reaction did not cause large absorbance changes but its oxidized form was revealed by a hitherto unknown electron spin resonance (ESR) signal, which had some properties of the well-known signal II but a linewidth and g-value much nearer to those of signal I. Upon darkening absorbance and ESR changes decayed together in a cyclic or back reaction which was stimulated by 3-(3,4 dichlorophenyl)-1,1-dimethylurea. The donor could be oxidized by ferricyanide in the dark. Illumination in the presence of ferricyanide induced absorbance and ESR changes, rapidly reversed upon darkening, which may be ascribed to the oxidation of a chlorophyll a dimer, possibly the primary electron donor of photosystem II. In addition an ESR signal with 15 to 20 gauss linewidth and a slower dark decay was observed, which may have been caused by a secondary donor.

Anderson TR, Slotkin TA. "Maturation of the adrenal medulla--IV. Effects of morphine." Biochem. Pharmacol.. 1975;24(16):1469-74.

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