Publications

SETTING

Antiretroviral therapy (ART) reduces pulmonary tuberculosis (PTB) in human immunodeficiency virus (HIV) infected children. Recent ART recommendations have increased the number of children on ART.

OBJECTIVE

To determine the prevalence and incidence of TB in HIV-infected children after the implementation of expanded ART guidelines.

DESIGN

A prospective cohort study including HIV-infected children aged 6 weeks to 14 years was conducted in Kenya. The primary outcome measure was clinically diagnosed TB. Study participants were screened for prevalent TB at enrollment using Kenya's national guidelines and followed at monthly intervals to detect incident TB. Predictors of TB were assessed using logistic regression and Cox proportional hazards regression.

RESULTS

Of 689 participants (median age 6.4 years), 509 (73.9%) were on ART at baseline. There were 51 cases of prevalent TB (7.4%) and 10 incident cases, with over 720.3 child-years of observation (incidence 1.4 per 100 child-years). Months on ART (adjusted hazard ratio [aHR] 0.91, P = 0.003; aOR 0.91, P< 0.001) and months in care before ART (aHR 0.87, P= 0.001; aOR 0.92, P < 0.001) were protective against incident and prevalent TB.

CONCLUSIONS

ART was protective against TB in this cohort of HIV-infected children with high levels of ART use. Optimal TB prevention strategies should emphasize early ART in children.

OBJECTIVE

To evaluate costs, cost-efficiency and cost-effectiveness of integration of family planning into HIV services.

INTERVENTION

Integration of family planning services into HIV care and treatment clinics.

DESIGN

A cluster-randomized trial.

SETTING

Twelve health facilities in Nyanza, Kenya were randomized to integrate family planning into HIV care and treatment; six health facilities were randomized to (nonintegrated) standard-of-care with separately delivered family planning and HIV services.

MAIN OUTCOME MEASURES

We assessed costs, cost-efficiency (cost per additional use of more effective family planning), and cost-effectiveness (cost per pregnancy averted) associated with the first year of integration of family planning into HIV care. More effective family planning methods included oral and injectable contraceptives, subdermal implants, intrauterine device, and female and male sterilization.

PATIENTS AND PARTICIPANTS

We collected cost data through interviews with study staff and review of financial records to determine costs of service integration.

RESULTS

Integration of services was associated with an average marginal cost of $841 per site and $48 per female patient. Average overall and marginal costs of integration were associated with personnel costs [initial ($1003 vs. $872) and refresher ($498 vs. $330) training, mentoring ($1175 vs. $902) and supervision ($1694 vs. $1636)], with fewer resources required for other fixed ($18 vs. $0) and recurring expenses ($471 vs. $287). Integration was associated with a marginal cost of $65 for each additional use of more effective family planning and $1368 for each pregnancy averted.

CONCLUSION

Integration of family planning and HIV services is feasible, inexpensive to implement, and cost-efficient in the Kenyan setting, and thus supports current Kenyan integration policy.

Program implementers and qualitative researchers have described how increasing availability of HIV antiretroviral therapy (ART) is associated with improvements in psychosocial health and internalized stigma. To determine whether, and through what channels, ART reduces internalized stigma, we analyzed data from 262 HIV-infected, treatment-naïve persons in rural Uganda followed from ART initiation over a median of 3.4 years. We fitted Poisson regression models with cluster-correlated robust estimates of variance, specifying internalized stigma as the dependent variable, adjusting for time on treatment as well as socio-demographic, clinical, and psychosocial variables. Over time on treatment, internalized stigma declined steadily, with the largest decline observed during the first 2 years of treatment. This trend remained statistically significant after multivariable adjustment (χ(2) = 28.3; P = 0.03), and appeared to be driven by ART-induced improvements in HIV symptom burden, physical and psychological wellbeing, and depression symptom severity.

OBJECTIVE

To assess the impact of pregnancy on mortality among HIV-infected Ugandan women initiating ART.

DESIGN

Prospective cohort study.

METHODS

HIV-infected women initiating ART in the Uganda AIDS Rural Treatment Outcomes study were assessed quarterly for self-reported pregnancy. The association between pregnancy and postpartum ('pregnancy-related') follow-up periods and mortality was assessed with Cox proportional hazards models adjusted for age, CD4 cell count, plasma HIV-1 RNA levels, and ART duration.

RESULTS

Three hundred and fifty-four women with median age 33 years (IQR: 27-37) and CD4 142 cells/μl (IQR: 82-213) were followed for a median of 4.0 years (IQR: 2.5-4.8) after ART initiation, with 3 and 7% loss-to-follow-up at years 1 and 5. One hundred and nine women experienced pregnancy. Five deaths occurred during pregnancy-related follow-up and 16 during nonpregnancy-related follow-up, for crude mortality rates during the first year after ART initiation of 12.57/100 PYs and 3.53/100 PYs (rate ratio 3.56, 95% CI: 0.97-11.07). In adjusted models, the impact of pregnancy-related follow-up on mortality was highest at ART initiation (aHR: 21.48, 95% CI: 3.73-123.51), decreasing to 13.44 (95% CI 3.28-55.11) after 4 months, 8.28 (95% CI 2.38-28.88) after 8 months, 5.18 (95% CI: 1.36-19.71) after 1 year, and 1.25 (95% CI: 0.10-15.58) after 2 years on ART. Four of five maternal deaths occurred postpartum.

CONCLUSION

Pregnancy and the postpartum period were associated with increased mortality in HIV-infected women initiating ART, particularly during early ART. Contraception proximate to ART initiation, earlier ART initiation, and careful monitoring during the postpartum period may reduce maternal mortality in this setting.

BACKGROUND

With aging, the probability of experiencing multiple chronic conditions has increased, along with symptoms associated with these conditions. Symptoms form a central component of illness burden, and distress. To date, most symptom measures have focused on a particular disease population.

OBJECTIVE

We aimed to develop and evaluate a simple symptom screen using data obtained from a representative sample of community-dwelling older adults.

METHODS

Psychometric analyses were conducted on 10 self-reported dichotomous symptom indicators collected during in-person interviews from a sample of 1000 community-dwelling older adults. Symptoms included shortness of breath, feeling tired or fatigued, problems with balance or dizziness, perceived weakness in legs, constipation, daily pain, stiffness, poor appetite, anxiety, and anhedonia.

RESULTS

Over one third of the individuals (37.4%) had 5 or more concurrent symptoms. Stiffness and feeling tired were the most common symptoms. Confirmatory factor analyses were performed on the 10 symptoms for single factor and bifactor (physical and affective) models of symptom reporting. Goodness-of-fit indices indicated better fit for the bifactor model (χdf=10=89.6; P<0.001), but the practical significance of the improvement in fit was negligible. Differential item functioning analyses showed some differences of relatively high magnitude in location parameters by race; however, because the differential item functioning was in different directions, the impact on the overall measure was most likely lessened.

CONCLUSIONS

Among community-dwelling older adults, a large proportion experienced multiple co-occurring symptoms. This Brief Symptom Screen can be used to quickly measure the overall symptom load in older adult populations, including those with multiple chronic conditions.

PURPOSE OF REVIEW

The advent of high-throughput whole-genome sequencing has the potential to revolutionize the conduct of outbreak investigation. Because of its ultimate resolution power for differentiating between closely related pathogen strains, whole-genome sequencing could augment the traditional epidemiologic investigations of infectious disease outbreaks.

RECENT FINDINGS

The combination of whole-genome sequencing and intensive epidemiologic analysis provided new insights on the sources and transmission dynamics of large-scale epidemics caused by Escherichia coli and Vibrio cholerae, nosocomial outbreaks caused by methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Mycobacterium abscessus, community-centered outbreaks caused by Mycobacterium tuberculosis, and natural disaster-associated outbreaks caused by environmentally acquired molds.

SUMMARY

When combined with traditional epidemiologic investigation, whole-genome sequencing has proven useful for elucidating the sources and transmission dynamics of disease outbreaks. Development of a fully automated bioinformatics pipeline for the analysis of whole-genome sequence data is much needed to make this powerful tool more widely accessible.

BACKGROUND

Survival rates for children diagnosed with Burkitt lymphoma (BL) in Africa are far below those achieved in developed countries. Late stage of presentation contributes to poor prognosis, therefore this study investigated factors leading to delays in BL diagnosis and treatment of children in Uganda and western Kenya.

METHODS

Guardians of children diagnosed with BL were interviewed at the Jaramogi Oginga Odinga Teaching and Referral Hospital (JTRH) and Uganda Cancer Institute (UCI) from Jan-Dec 2010. Information on sociodemographics, knowledge, attitudes, illness perceptions, health-seeking behaviors and prior health encounters was collected using a standardized, pre-tested questionnaire.

RESULTS

Eighty-two guardians were interviewed (20 JTRH, 62 UCI). Median "total delay" (1st symptoms to BL diagnosis) was 12.1 weeks [interquartile range (IQR) 4.9-19.9] in Kenya and 12.9 weeks (IQR 4.3-25.7) in Uganda. In Kenya, median "guardian delay" (1st symptoms to 1st health encounter) and "health system delay" (1st health encounter to BL diagnosis) were 9.0 weeks (IQR 3.6-15.7) and 2.0 weeks (IQR 1.6-5.8), respectively. Data on guardian and health system delay in Uganda were only available for those with < 4 prior health encounters (n = 26). Of these, median guardian delay was 4.3 weeks (range 0.7-149.9), health system delay 2.6 weeks (range 0.1-16.0), and total delay 10.7 weeks (range 1.7-154.3). Guardians in Uganda reported more health encounters than those in Kenya (median 5, range 3-16 vs. median 3, range 2-6). Among Kenyan guardians, source of income was the only independent predictor of delay, whereas in Uganda, guardian delay was influenced by guardians' beliefs on the curability of cancer, health system delay, by guardians' perceptions of cancer as a contagious disease, and total delay, by the number of children in the household and guardians' role as caretaker. Qualitative findings suggest financial costs, transportation, and other household responsibilities were major barriers to care.

CONCLUSIONS

Delays from symptom onset to BL treatment were considerable given the rapid growth rate of this cancer, with guardian delay constituting the majority of total delay in both settings. Future interventions should aim to reduce structural barriers to care and increase awareness of BL in particular and cancer in general within the community, as well as among health professionals.

Staphylococcus saprophyticus is the only species of Staphylococcus that is typically uropathogenic and possesses a gene coding for a D-serine-deaminase (DsdA). As D-serine is prevalent in urine and toxic or bacteriostatic to many bacteria, it is not surprising that the D-serine-deaminase gene is found in the genome of uropathogens. It has been suggested that D-serine-deaminase or the ability to respond to or to metabolize D-serine is important for virulence. For uropathogenic Escherichia coli (UPEC), a high intracellular D-serine concentration affects expression of virulence factors. S. saprophyticus is able to grow in the presence of high D-serine concentrations; however, its D-serine metabolism has not been described. The activity of the D-serine-deaminase was verified by analyzing the formation of pyruvate from D-serine in different strains with and without D-serine-deaminase. Cocultivation experiments were performed to show that D-serine-deaminase confers a growth advantage to S. saprophyticus in the presence of D-serine. Furthermore, in vivo coinfection experiments showed a disadvantage for the ΔdsdA mutant during urinary tract infection. Expression analysis of known virulence factors by reverse transcription-quantitative PCR (RT-qPCR) showed that the surface-associated lipase Ssp is upregulated in the presence of D-serine. In addition, we show that S. saprophyticus is able to use D-serine as the sole carbon source, but interestingly, D-serine had a negative effect on growth when glucose was also present. Taken together, D-serine metabolism is associated with virulence in S. saprophyticus, as at least one known virulence factor is upregulated in the presence of D-serine and a ΔdsdA mutant was attenuated in virulence murine model of urinary tract infection.