Causes of preterm and low birth weight neonatal mortality in a rural community in Kenya: evidence from verbal and social autopsy.

BACKGROUND: Under-five mortality in Kenya has declined over the past two decades. However, the reduction in the neonatal mortality rate has remained stagnant. In a country with weak civil registration and vital statistics systems, there is an evident gap in documentation of mortality and its causes among low birth weight (LBW) and preterm neonates. We aimed to establish causes of neonatal LBW and preterm mortality in Migori County, among participants of the PTBI-K (Preterm Birth Initiative-Kenya) study. METHODS: Verbal and social autopsy (VASA) interviews were conducted with caregivers of deceased LBW and preterm neonates delivered within selected 17 health facilities in Migori County, Kenya. The probable cause of death was assigned using the WHO International Classification of Diseases (ICD-10). RESULTS: Between January 2017 to December 2018, 3175 babies were born preterm or LBW, and 164 (5.1%) died in the first 28 days of life. VASA was conducted among 88 (53.7%) of the neonatal deaths. Almost half (38, 43.2%) of the deaths occurred within the first 24 h of life. Birth asphyxia (45.5%), neonatal sepsis (26.1%), respiratory distress syndrome (12.5%) and hypothermia (11.0%) were the leading causes of death. In the early neonatal period, majority (54.3%) of the neonates succumbed to asphyxia while in the late neonatal period majority (66.7%) succumbed to sepsis. Delay in seeking medical care was reported for 4 (5.8%) of the neonatal deaths. CONCLUSION: Deaths among LBW and preterm neonates occur early in life due to preventable causes. This calls for enhanced implementation of existing facility-based intrapartum and immediate postpartum care interventions, targeting asphyxia, sepsis, respiratory distress syndrome and hypothermia.

Mode of delivery and postpartum HIV-1 disease progression and mortality in a Kenyan cohort.

BACKGROUND: There are limited data on the impact of cesarean section delivery on HIV-1 infected women in Sub-Saharan Africa. The purpose of this study was to assess the effect of mode of delivery on HIV-1 disease progression and postpartum mortality in a Kenyan cohort. METHODS: A prospective cohort study was conducted in Nairobi, Kenya from 2000-2005. We determined changes in CD4+ counts, HIV-1 RNA levels and mortality during the first year postpartum between HIV-1 infected women who underwent vaginal delivery (VD), non-scheduled cesarean section (NSCS) and scheduled cesarean section (SCS) and received short-course zidovudine. Loess curves and multivariate linear mixed effects models were used to compare longitudinal changes in maternal HIV-1 RNA and CD4+ counts by mode of delivery. Kaplan Meier curves, the log rank test, and Cox proportional hazards regression were used to assess difference in mortality. RESULTS: Of 501 women, 405 delivered by VD, 74 delivered by NSCS and 22 by SCS. Baseline characteristics were similar between the VD and NSCS groups. Baseline antenatal CD4+ counts were lowest and HIV-1 RNA levels highest in the NSCS group but HIV-1 RNA levels were similar between groups at delivery. The rate of decline in CD4+ cells and rate of increase in HIV-1 RNA did not differ between groups. After adjusting for confounders, women who underwent NSCS had a 3.39-fold (95% CI 1.11, 10.35, P = 0.03) higher risk of mortality in the first year postpartum compared to women with VD. CONCLUSIONS: Non-scheduled cesarean section was an independent risk factor for postpartum mortality in HIV-1 positive Kenyan women. The cause of death was predominantly due to HIV-1 related infections, and not direct maternal deaths, however, this was not mirrored by differential changes in HIV-1 progression markers between the groups.

Evaluation of impact of long-lasting insecticide-treated bed nets and point-of-use water filters on HIV-1 disease progression in Kenya.

OBJECTIVES: Among HIV-1-infected individuals in Africa, coinfection with malaria and diarrhoeal disease may be associated with more rapid HIV-1 disease progression. We sought to determine whether the use of long-lasting insecticide-treated bed nets and simple point-of-use water filters can delay HIV-1 disease progression. DESIGN: A prospective cohort study. SETTING: Two HIV care sites in Kenya. PARTICIPANTS: HIV-1-infected adults not yet meeting criteria for antiretroviral therapy. INTERVENTIONS: One group received the standard of care, whereas the other received long-lasting insecticide-treated bed nets and water filters. Individuals were followed for up to 24 months. MAIN OUTCOME MEASURES: The primary outcome measures were time to CD4 cell count less than 350 cells/µl and a composite endpoint of time to CD4 cell count less than 350 cells/µl and nontraumatic death. Time to disease progression was compared using Cox proportional hazards regression. RESULTS: Of 589 individuals included, 361 received the intervention and 228 served as controls. Median baseline CD4 cell counts were similar (P=0.36). After controlling for baseline CD4 cell count, individuals receiving the intervention were 27% less likely to reach the endpoint of a CD4 cell count less than 350 cells/µl (hazard ratio 0.73; 95% confidence interval 0.57-0.95). CD4 cell count decline was also significantly less in the intervention group (-54 vs. -70 cells/µl per year, P=0.03). In addition, the incidence of malaria and diarrhoea were significantly lower in the intervention group. CONCLUSION: Provision of a long-lasting insecticide-treated bed net and water filter was associated with a delay in CD4 cell count decline and may be a simple, practical and cost-effective strategy to delay HIV-1 progression in many resource-limited settings.

Prevalence and correlates of insecticide-treated bednet use among HIV-1-infected adults in Kenya.

HIV-1-infected adults are at increased risk for malaria. Insecticide-treated bednets protect individuals from malaria. Little is known about correlates of ownership and use of bednets among HIV-1-infected individuals. We conducted a cross-sectional survey of 388 HIV-1-infected adults recruited from three sites in Kenya (Kilifi, Kisii, and Kisumu) to determine factors associated with ownership and use of optimal bednets. We defined an optimal bednet as an untorn, insecticide-treated bednet. Of 388 participants, 134(34.5%) reported owning an optimal bednet. Of those that owned optimal bednets, most (76.9%) reported using it daily. In a multivariate model, higher socioeconomic status as defined as postsecondary education [OR = 2.8 (95% CI: 1.3-6.4), p = 0.01] and living in a permanent home [OR = 1.7(1.03-2.9), p = 0.04] were significantly associated with optimal bednet ownership. Among individuals who owned bednets, employed individuals were less likely [OR = 0.2(0.04-0.8), p = 0.01] and participants from Kilifi were more likely to use bednets [OR = 2.9 (95% CI 1.04-8.1), p = 0.04] in univariate analysis. Participants from Kilifi had the least education, lowest income, and lowest rate of employment. Our findings suggest that lower socioeconomic status is a barrier to ownership of an optimal bednet. However, consistent use is high once individuals are in possession of an optimal bednet. Increasing access to optimal bednets will lead to high uptake and use.

Herpes simplex virus type 2, genital ulcers and HIV-1 disease progression in postpartum women.

BACKGROUND: Co-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear. METHODS: HIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12-24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI), and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression. RESULTS: Among 296 women, 254 (86%) were HSV-2-seropositive. Only 30 (10%) women had prior or current genital ulcer disease (GUD); median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR) 2.79, 95% CI: 1.33-5.85), and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93-15.83). Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07). CONCLUSIONS: HSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2.

Determinants of failure to access care in mothers referred to HIV treatment programs in Nairobi, Kenya.

BACKGROUND: As prevention of mother-to-child transmission of HIV (PMTCT) programs and HIV treatment programs rapidly expand in parallel, it is important to determine factors that influence the transition of HIV-infected women from maternal to continuing care. DESIGN: This study aimed to determine rates and co-factors of accessing HIV care by HIV-infected women exiting maternal care. A cross-sectional survey of women who had participated in a PMTCT research study and were referred to care programs in Nairobi, Kenya was conducted. METHODS: A median of 17 months following referral, women were located by peer counselors and interviewed to determine whether they accessed HIV care and what influenced their care decisions. Fisher's exact test was used to assess the association between client characteristics and access to care. RESULTS: Peer counselors traced 195 (82%) residences, where they located 116 (59%) participants who provided information on care. Since exit, 50% of participants had changed residence, and 74% reported going to the referral HIV program. Reasons for not accessing care included lack of money, confidentiality, and dislike of the facility. Women who did not access care were less likely to have informed their partner of the referral (p=0.001), and were less likely believe that highly active antiretroviral therapy (HAART) is effective (p<0.01). Among those who accessed care, 33% subsequently discontinued care, most because they did not qualify for HAART. Factors cited as barriers to access included stigma, denial, poor services, and lack of money. Factors that were cited as making care attractive included health education, counseling, free services, and compassion. CONCLUSION: A substantial number of women exiting maternal care do not transit to HIV care programs. Partner involvement, a standardized referral process and more comprehensive HIV education for mothers diagnosed with HIV during pregnancy may facilitate successful transitions between PMTCT and HIV care programs.

Prevalence and correlates of helminth co-infection in Kenyan HIV-1 infected adults.

BACKGROUND: Deworming HIV-1 infected individuals may delay HIV-1 disease progression. It is important to determine the prevalence and correlates of HIV-1/helminth co-infection in helminth-endemic areas. METHODS: HIV-1 infected individuals (CD4>250 cells/ul) were screened for helminth infection at ten sites in Kenya. Prevalence and correlates of helminth infection were determined. A subset of individuals with soil-transmitted helminth infection was re-evaluated 12 weeks following albendazole therapy. RESULTS: Of 1,541 HIV-1 seropositive individuals screened, 298 (19.3%) had detectable helminth infections. Among individuals with helminth infection, hookworm species were the most prevalent (56.3%), followed by Ascaris lumbricoides (17.1%), Trichuris trichiura (8.7%), Schistosoma mansoni (7.1%), and Strongyloides stercoralis (1.3%). Infection with multiple species occurred in 9.4% of infections. After CD4 count was controlled for, rural residence (RR 1.40, 95% CI: 1.08-1.81), having no education (RR 1.57, 95% CI: 1.07-2.30), and higher CD4 count (RR 1.36, 95% CI: 1.07-1.73) remained independently associated with risk of helminth infection. Twelve weeks following treatment with albendazole, 32% of helminth-infected individuals had detectable helminths on examination. Residence, education, and CD4 count were not associated with persistent helminth infection. CONCLUSIONS: Among HIV-1 seropositive adults with CD4 counts above 250 cells/mm(3) in Kenya, traditional risk factors for helminth infection, including rural residence and lack of education, were associated with co-infection, while lower CD4 counts were not.

Albendazole treatment of HIV-1 and helminth co-infection: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Several co-infections have been shown to impact the progression of HIV-1 infection. We sought to determine if treatment of helminth co-infection in HIV-1-infected adults impacted markers of HIV-1 disease progression. DESIGN: To date, there have been no randomized trials to examine the effects of soil-transmitted helminth eradication on markers of HIV-1 progression. METHODS: A randomized, double-blind, placebo-controlled trial of albendazole (400 mg daily for 3 days) in antiretroviral-naive HIV-1-infected adults (CD4 cell count >200 cells/microl) with soil-transmitted helminth infection was conducted at 10 sites in Kenya (ClinicalTrials.gov NCT00130910). CD4 and plasma HIV-1 RNA levels at 12 weeks following randomization were compared in the trial arms using linear regression, adjusting for baseline values. RESULTS: Of 1551 HIV-1-infected individuals screened for helminth infection, 299 were helminth infected. Two hundred and thirty-four adults were enrolled and underwent randomization and 208 individuals were included in intent-to-treat analyses. Mean CD4 cell count was 557 cells/microl and mean plasma viral load was 4.75 log10 copies/ml at enrollment. Albendazole therapy resulted in significantly higher CD4 cell counts among individuals with Ascaris lumbricoides infection after 12 weeks of follow-up (+109 cells/microl; 95% confidence interval +38.9 to +179.0, P = 0.003) and a trend for 0.54 log10 lower HIV-1 RNA levels (P = 0.09). These effects were not seen with treatment of other species of soil-transmitted helminths. CONCLUSION: Treatment of A. lumbricoides with albendazole in HIV-1-coinfected adults resulted in significantly increased CD4 cell counts during 3-month follow-up. Given the high prevalence of A. lumbricoides infection worldwide, deworming may be an important potential strategy to delay HIV-1 progression.

Morbidity among HIV-1-infected mothers in Kenya: prevalence and correlates of illness during 2-year postpartum follow-up.

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.

Hormonal contraception and HIV-1 disease progression among postpartum Kenyan women.

OBJECTIVE: To assess the immediate and longer-term effects of the use of hormonal contraception on the progression of HIV-1 disease in postpartum women. DESIGN: A prospective cohort study. METHODS: Information on contraceptive use, breastfeeding and intercurrent illnesses was obtained from HIV-infected postpartum Kenyan women monthly in the first year postpartum and quarterly in the second year. Blood was collected for T-cell subset analyses and HIV-1-RNA levels at months 1, 3, 6, 9, 12, 18, and 24 postpartum. The immediate effect of the initiation of oral contraceptive pills (OCP) and depot medroxyprogesterone acetate (DMPA) was assessed by comparing the change in the HIV-1-RNA plasma viral load and CD4 T-cell counts among women remaining off these contraceptive methods with those initiating them. The longer-term effects of OCP and DMPA on disease progression were assessed using Loess curves and linear mixed effects models to compare changes over the first 24 months postpartum in these same disease progression markers. RESULTS: There were no significant immediate or longer-term effects of the use of OCP or DMPA on HIV-1-RNA plasma viral loads and CD4 T-cell counts in this cohort of HIV-infected postpartum Kenyan women. CONCLUSION: Comprehensive contraceptive counselling for HIV-1-infected women requires an understanding of the effects of various contraceptive methods on HIV-1 disease progression. In this study, hormonal contraception reassuringly had no immediate or longer-term effects on the rate of disease progression in chronically HIV-1-infected postpartum women. This highly effective family planning method may provide a useful and safe option for the prevention of mother-to-child transmission of HIV-1.

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.

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/ microL/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/ microL/month) than in mothers who never breast-fed (4.0 cells/ microL/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.

Predictors of early mortality in a cohort of human immunodeficiency virus type 1-infected african children.

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