Association of in utero antibiotic exposure on childhood ear infection trajectories: Results from a national birth cohort study.

AIM: Most prescribed medicines during pregnancy are antibiotics, with unknown effects on a fetus and on the infant's acquired microbiome. This study investigates associations between in utero antibiotic exposure and ear infection trajectories over the first decade of life, hypothesising effects on early or persistent, rather than later-developing, ear infections. METHODS: Design and participants: The Longitudinal Study of Australian Children birth cohort recruited a nationally-representative sample of 5107 infants in 2004. MEASURES: Mothers reported antibiotic use in pregnancy when a child was 3-21 months old (wave 1), and ongoing problems with ear infection every 2 years spanning ages 0-1 to 10-11 years (waves 1-6). ANALYSIS: Latent class models identified ear infection trajectories, and univariable and multivariable multinomial logistic regression determined odds of adverse trajectories by antibiotic exposure. RESULTS: A total of 4500 (88.1% of original sample) children contributed (mean baseline age 0.7 years; 51.3% boys); 10.4% of mothers reported antibiotic use in pregnancy. Four probability trajectories for ear infection emerged: 'consistently low' (86.2%), 'moderate to low' (5.6%), 'low to moderate' (6.7%) and 'consistently high' (1.4%). Antibiotic use in pregnancy was associated with children following 'consistently high' (adjusted odds ratio 2.04, 95% confidence interval 1.08-3.88, P = 0.03) and 'moderate to low' (adjusted odds ratio 1.78, 95% confidence interval 1.25-2.53, P = 0.001) trajectories. CONCLUSIONS: Antibiotic use in pregnancy is associated with an increased risk of persistent and early childhood ear infections. This highlights the wisdom of cautious antibiotic use during pregnancy, and the need for the study of potential mechanisms underlying these associations.

Intimate partner violence and utilization of maternal health care services in Addis Ababa, Ethiopia.

BACKGROUND: Despite its prominence, intimate partner violence (IPV) against women has received little attention in Ethiopia. And as many of sub-Saharan African countries, maternal health care services utilization remains poor. Full access and utilization of maternal health care services is a key to significant reduction in maternal and child mortality, and eliminate new HIV infection in infants. Identifying the factors that contribute to the poor access and utilization should aid the design of appropriate policy and intervention strategies. Thus the objective of this study was to examine the association between IPV and use of maternal health care services in Addis Ababa, Ethiopia. METHODS: A cross sectional study on couples (N = 210; male/female pairs) with an infant less than 6 months of age was conducted. The dependent variable was use of maternal health care services and the main independent variable was IPV. Data was collected using face-to-face self-reported questionnaires and analyzed using SPSS version 20.0. Bivariate and multivariate logistic regression models were used to examine the relationship between the dependent and independent variables. RESULTS: The mean age of the women was 28.7 years (SD = 5.4), on average women were 7.4 years (SD = 7.4) younger than their partners. Although most of the women (95.2%) had at least one antenatal care (ANC), only 35 (2%) had ≥4 ANC visits and about half (49.0%) had their first ANC visit within the first trimester. Women who experienced emotional IPV in their relationship were less likely to have their 1st ANC within three months of pregnancy (AOR = 0.69; 95%CI = 0.49-0.96). Women who reported physical IPV in their relationship were less likely to use ≥4 ANC (AOR = 0.48; 95%CI = 0.21-0.71), be tested for HIV (AOR = 0.26; 95%CI = 0.09-0.79), have skilled delivery attendant (AOR = 0.31; 95%CI = 0.12-0.98), and deliver in a health facility (AOR = 0.35; 95%CI = 0.14-0.88). Likewise, women experienced sexual IPV or partner control in their relationship were less likely to use ANC ≥4 times (AORsexual-IPV = 0.91; 95%CI = 0.84-0.98 and AORpartner-control = 0.38; 95%CI = 0.17-0.85 respectively). CONCLUSIONS: IPV is prevalent among couples in Addis Ababa, Ethiopia where three out of four women reported having experienced one or more type of IPV in their current relationship. And all types of IPV showed significant association with poor utilization of one or more maternal health care services. Thus efforts to sustain the recent success in maternal health and further improvement should give due consideration to IPV.

Expansion of HIV care and treatment in Yunnan Province, China: treatment outcomes with scale up of combination antiretroviral therapy.

Effective health care models to scale up combination antiretroviral therapy (ART) are needed in rural southwestern China. We aimed to evaluate the ART treatment outcomes and their associations with patients' demographic characteristics and pre-treatment clinical features in a scaled-up provincial ART program serving eight heavily HIV-affected prefectures in Yunnan Province. We abstracted information from a computerized database for adults initiating ART between July 2007 and September 2008. Survival functions of mortality and treatment failure were calculated by age group, gender, transmission mode, and baseline CD4 count. Multivariable Cox regression analyses were conducted to find independent associations of various demographic and baseline clinical features with outcome variables. Of the 1967 patients in the mortality analysis, there were 110 deaths, of which 16 were coded as accidents or suicides. Adjusted hazard ratios (AHR) associated with mortality were greater for patients with baseline CD4 counts <100 cells/µl vs. patients with CD4 counts ≥200 cells/µl, for male vs. female, for single vs. married, and for those acquired HIV through injection drug use (IDU) vs. other modes of transmission. Successful treatment was 81.3% at six months after treatment started. Immunologic treatment failure was associated with baseline CD4 counts but not with demographic characteristics. Overall loss to follow-up rate was 2.1%. Collaboration between clinics and community networks are distinctive features of Yunnan's model for scaling up ART across a diverse, poor, and rural population. This study finds that the strategy can succeed even if 40% of the patients have a history of IDU.

Prediction of treatment failure using 2010 World Health Organization Guidelines is associated with high misclassification rates and drug resistance among HIV-infected Cambodian children.

BACKGROUND: Antiretroviral therapy (ART) in resource-limited settings (RLSs) is monitored clinically and immunologically, according to World Health Organization (WHO) or national guidelines. Revised WHO pediatric guidelines were published in 2010, but their ability to accurately identify virological failure is unclear. METHODS: We evaluated performance of WHO 2010 guidelines and compared them with WHO 2006 and Cambodia 2011 guidelines among children on ≥6 months of first-line ART at Angkor Hospital for Children between January 2005 and September 2010. We determined sensitivity, specificity, positive and negative predictive values, and accuracy using bootstrap resampling to account for multiple tests per child. Human immunodeficiency virus (HIV) resistance was compared between those correctly and incorrectly identified by each guideline. RESULTS: Among 457 children with 1079 viral loads (VLs), 20% had >400 copies/mL. For children with WHO stage 1/2 HIV, misclassification as failure (met CD4 failure criteria, but VL undetectable) was 64% for WHO 2006 guidelines, 33% for WHO 2010 guidelines, and 81% for Cambodia 2011 guidelines; misclassification as success (did not meet CD4 failure, but VL detectable) was 11%, 12%, and 12%, respectively. For children with WHO stage 3/4 HIV, misclassification as failure was 35% for WHO 2006 guidelines, 40% for WHO 2010 guidelines, and 43% for Cambodia 2011 guidelines; misclassification as success was 13%, 24%, and 21%, respectively. Compared with WHO 2006 guidelines, WHO 2010 guidelines significantly increased the risk of misclassification as success in stage 3/4 HIV (P < .05). The WHO 2010 guidelines failed to identify 98% of children with extensive reverse-transcriptase resistance. CONCLUSIONS: In our cohort, lack of virological monitoring would result in unacceptable treatment failure misclassification, leading to premature ART switch and resistance accumulation. Affordable virological monitoring suitable for use in RLSs is desperately needed.

Growth of infants born to HIV-infected women in South Africa according to maternal and infant characteristics.

OBJECTIVE: To evaluate growth parameters assessed by weight and length in HIV-infected and HIV-uninfected infants born to HIV-infected mothers in South Africa from birth to 6 months of age. METHODS: We calculated z-scores for weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) among a cohort of 840 mother-infant dyads. Multivariable Cox proportional hazards models with time-varying covariates were used to estimate the risk of falling <-2 z-scores for WAZ, LAZ, and WLZ as a function of infant and maternal characteristics. RESULTS: By 6 months after birth, a fifth of infants had WAZ <-2, 19% had an LAZ <-2, and 29% had a WLZ <-2. WLZ and WAZ were significantly lower in HIV-infected infants than in uninfected infants by 3 months of age and LAZ by 6 months of age (P<0.001). The risk of WAZ falling <-2 was associated with decreasing maternal CD4 cell count (adj. HR for CD4 cell count <200 cells/µl: 1.64; 95% CI: 1.10-2.43), premature birth (adj. HR: 2.82; 95% CI: 2.06-3.86) and formula feeding (adj. HR: 3.35; 95% CI: 1.64-6.85). The risk of LAZ falling <-2 was associated with increasingly lower maternal age (adj. HR for<20 years: 0.54; 95% CI: 0.31-0.96), lower maternal CD4 cell count (adj. HR for CD4 cell count <200 cells/µl: 1.72; 95% CI: 1.14-2.59), premature birth (adj. HR: 2.37; 95% CI: 1.70-3.30) and formula feeding (adj. HR: 4.22; 95% CI: 1.85-9.62). The risk of WLZ falling <-2 was significantly associated with infant HIV infection (adj. HR: 1.64; 95% CI: 1.16-2.32) and formula feeding (adj. HR: 1.78; 95% CI: 1.11-2.83). The risk of WAZ and LAZ falling <-2 was more than two times greater for HIV-infected infants than for uninfected infants with gastrointestinal infections. CONCLUSIONS: HIV-infected infants were more likely to be stunted and wasted than uninfected infants, which often occurred within 3 months after birth. Infants who were born to mothers with advanced HIV disease, formula-fed and co-infected with HIV and gastrointestinal infections were at greater risk for growth disturbances. Further interventions are needed to promptly initiate both HIV-infected mothers and infants on appropriate antiretroviral therapy and nutritional supplementation.

Drug rash, eosinophilia, and systemic symptoms syndrome: Two pediatric cases demonstrating the range of severity in presentation--A case of vancomycin-induced drug hypersensitivity mimicking toxic shock syndrome and a milder case induced by minocycline.

BACKGROUND: Drug rash, eosinophilia, and systemic symptoms syndrome is a type of drug hypersensitivity reaction characterized by the clinical triad of skin eruption, fever, and internal organ involvement. Drug rash, eosinophilia, and systemic symptoms syndrome has rarely been reported in association with vancomycin or in the pediatric population. There have only been four pediatric case reports of drug rash, eosinophilia, and systemic symptoms syndrome and three cases of drug rash, eosinophilia, and systemic symptoms syndrome involving vancomycin published in the English literature to date. CASE REPORTS: We describe two pediatric cases of drug rash, eosinophilia, and systemic symptoms syndrome to illustrate the range in severity of presentation. The first case illustrates drug rash, eosinophilia, and systemic symptoms syndrome associated with vancomycin exposure in a 14-yr-old boy with Duchenne muscular dystrophy after posterior spinal fusion, whose clinical presentation was indistinguishable from toxic shock syndrome. The second case illustrates a milder and more typical presentation of drug rash, eosinophilia, and systemic symptoms syndrome in a 14-yr-old boy being treated with minocycline for acne. We also present a review of the literature relevant to this syndrome. CONCLUSIONS: : Drug rash, eosinophilia, and systemic symptoms syndrome is relatively unknown among general pediatricians and pediatric intensivists and may potentially become more common with the increasing use of long-term medications in the pediatric population. Our cases demonstrate the importance of an awareness of drug rash, eosinophilia, and systemic symptoms syndrome among general pediatricians and pediatric intensivists because drug rash, eosinophilia, and systemic symptoms syndrome may present in any range of severity, from indolent illness to frank and refractory shock.

Advanced HIV: diagnosis, treatment, and prevention.

Substantial progress has been made this century in bringing millions of people living with HIV into care, but progress for early HIV diagnosis has stalled. Individuals first diagnosed with advanced HIV have higher rates of mortality than those diagnosed at an earlier stage even after starting antiretroviral therapy (ART), resulting in substantial costs to health systems. Diagnosis of these individuals is hindered because many patients are asymptomatic, despite being severely immunosuppressed. Baseline CD4 counts and screening for opportunistic infections, such as tuberculosis and cryptococcus, is crucial because of the high mortality associated with these co-infections. Individuals with advanced HIV should have rapid ART initiation (except when found to have symptoms, signs, or a diagnosis of cryptococcal meningitis) and those in treatment failure should switch treatment. Overcoming barriers to testing and adherence through the development of differentiated care models and providing psychosocial support will be key in reaching populations at high risk of presenting with advanced HIV.

Directly observed highly active antiretroviral therapy for HIV-infected children in Cambodia.

Antiretroviral medications are becoming available for HIV-infected children in resource-limited settings. Maryknoll, an international Catholic charity, provided directly observed antiretroviral therapy to HIV-infected children in Phnom Penh, Cambodia. Child care workers administered generic antiretroviral drugs twice daily to children, ensuring adherence. Treatment began with 117 late-stage HIV-infected children; 22 died of AIDS during the first 6 months. The rest were treated for at least 6 months and showed CD4 count increases comparable to those achieved in US and European children. Staffing cost for this program was approximately US $5 per child per month, or 15% more than the price of the medications. Drug toxicities were uncommon and easily managed. Directly observed antiretroviral therapy appears to be a promising, low-cost strategy for ensuring adherent treatment for HIV-infected children in a resource-limited setting.

Etiology of chronic diarrhea in antiretroviral-naive patients with HIV infection admitted to Norodom Sihanouk Hospital, Phnom Penh, Cambodia.

BACKGROUND: Although both human immunodeficiency virus (HIV) infection and diarrhea are considerable problems in Cambodia, there have not been any studies to determine the history, clinical presentation, and etiology of chronic diarrhea in patients with HIV infection in Cambodia. In this article, we present a case-control study involving 40 HIV-infected patients with chronic diarrhea and 40 HIV-infected patients without diarrhea. METHODS: Clinical, demographic, and laboratory data were collected. Stool samples were examined for parasites, including Cryptosporidium species (by partial acid-fast stain), bacterial pathogens, and rotavirus. Samples from 10 case patients and 10 control subjects were also analyzed for Cryptosporidium species by polymerase chain reaction-restriction fragment-length polymorphism. RESULTS: The median CD4(+) cell count was 11.5 cells/mm(3). A potential pathogen was found in 30 case patients (75%) and 29 control subjects (72.5%). Cryptosporidium was the most common pathogen, present in 16 case patients (40%) and 20 control subjects (53.3%). The presence of Cryptosporidium was confirmed by polymerase chain reaction-restriction fragment-length polymorphism, with a prevalence of 40% in each of the 2 groups of 10 subjects who were enrolled for Cryptosporidium evaluation. CONCLUSIONS: Subjects in this cohort had severe immunosuppression. The prevalence of pathogens, including Cryptosporidium, was extremely high but did not differ significantly between the case patients with diarrhea and the control subjects without diarrhea. Further studies are needed to examine factors associated with Cryptosporidium carriage and the natural history of asymptomatic infection.

Demographic and clinical characteristics of HIV-infected inpatients and outpatients at a Cambodian hospital.

A retrospective cross-sectional survey of 299 HIV-infected inpatients and outpatients was conducted between March 1999 and June 2000 in Phnom Penh, Cambodia, to define patient demographics and risk factors for HIV-1 infection, and to compare whether symptoms and opportunistic infections (OIs) differ by gender and site of patient care. The population represented one third of HIV-infected patients regularly receiving care at the Sihanouk Hospital Center of HOPE. Over one quarter (26%) of the men were soldiers and 27% were farmers or laborers. Eighty-nine percent of the men had visited sex workers, 29% of men and women had unsafe injections in the past, and 18% of women reported a spouse who was HIV-positive. Eighty percent of patients presented with weight loss more than 10% from baseline. Seventy-two percent of patients were diagnosed with two or more concurrent OIs or conditions. Oral candidiasis (p = <0.001), abdominal lymphadenitis (p = 0.03), and two or more concurrent OIs (p = <0.001) were diagnosed more often among men than women. Multivariate logistic regression shows that patients who presented with weight loss more than 10% from baseline are more likely to have one or more OIs or conditions. The results of this survey suggest that the primary risk factor for HIV-infected men presenting to this care facility was visiting sex workers. The pattern of OIs and other HIV-associated conditions indicated that the majority of patients delayed seeking care at the hospital. HIV physicians in Cambodia should be aware of the likelihood for multiple OIs or conditions when patients present weight loss more than 10% from baseline.

Interventions to reduce childhood antibiotic prescribing for upper respiratory infections: systematic review and meta-analysis.

BACKGROUND: Antibiotics are overprescribed for children with upper respiratory infections (URIs), leading to unnecessary expenditures, adverse events and antibiotic resistance. This study assesses whether interventions antibiotic prescription rates (APR) for childhood URIs can be reduced and what factors impact intervention effectiveness. METHODS: MEDLINE, Embase, Google Scholar, Web of Science, Global Health, WHO website, United States CDC website and The Cochrane Central Register of Controlled Trials (CENTRAL) were searched by December 2015. Cluster or individual-patient randomised controlled trials (RCTs) and non-RCTs that examined interventions to change APR for children with URIs were selected for meta-analysis. Educational interventions for clinicians and/or parents were compared with usual care. RESULTS: Of 6074 studies identified, 13 were included. All were conducted in high-income countries. Interventions were associated with lower APR versus usual care (OR 0.63 (95% CI 0.50 to 0.81, p<0.001). A patient-clinician communication approach was the most effective type of intervention, with a pooled OR 0.41 (95% CI 0.20 to 0.83; p<0.001) for clinicians and 0.26 (95% CI 0.08 to 0.91; p=0.04) for parents. Interventions that targeted clinicians and parents were significant, with a pooled OR of 0.52 (95% CI 0.35 to 0.78; p=0.002). Insignificant effects were observed for targeting clinicians and parents alone, with a pooled OR of 0.88 (95% CI 0.67 to 1.16; p=0.37) and 0.50 (95% CI 0.10 to 2.51, p=0.40), respectively. CONCLUSIONS: Educational interventions are effective in reducing antibiotic prescribing for childhood URIs. Interventions targeting clinicians and parents are more effective than those for either group alone. The most effective interventions address patient-clinician communication. Studies in low-income to middle-income countries are needed.

Directly observed antiretroviral therapy to reduce genital tract and plasma HIV-1 RNA in women with poor adherence.

Six women with substance abuse and poor adherence histories received daily antiretroviral directly observed therapy (DOT). Cervicovaginal lavage (CVL) and plasma HIV-1-RNA levels were measured at baseline, 1 month, 3 months, and 6 months. All subjects had undetectable (below 2.6 log10 copies/ml) CVL HIV-1-RNA levels by 3 months and undetectable plasma HIV-1-RNA levels by 6 months. The mean CD4 cell increase was 76 cells/mm3. DOT appears effective and may reduce infectiousness in this high-risk population.

A pilot study of treatment of bacterial vaginosis with a buffering vaginal microbicide.

BACKGROUND: Bacterial vaginosis (BV) is an extremely common problem for women and is associated with adverse pregnancy outcomes and HIV infection. Currently available antibiotic treatments are moderately effective but may need to be repeated frequently because of the recurrent nature of the disease. We undertook a pilot study of a buffering vaginal microbicide in the treatment of BV. METHODS: Women with clinically diagnosed BV were recruited to receive seven applications (5 g per application) of BufferGel trade mark (ReProtect, LLC, Baltimore, MD), a topical vaginal microbicide, and had clinical and gram stain evaluation of response. Subjects were evaluated at 2-3 days after the last application of BufferGel as a test of cure and again at 1 month to assess for relapse. Subjects with BV at test of cure were offered oral metronidazole. RESULTS: Thirty-one women were screened, 16 were offered enrollment, and 10 completed the study. Treatment with BufferGel was clinically effective in 70% of women at 2-3 days after treatment and in 40% of women by 1-month follow-up. CONCLUSIONS: These results suggest that 5 g of BufferGel vaginally once a day appears to be a moderately effective treatment for BV.

Spectrum of opportunistic infections in hospitalized HIV-infected patients in Phnom Penh, Cambodia.

The aim of the study was to provide more comprehensive data on the clinical characteristics of hospitalized AIDS patients in Cambodia. Chart review of 381 HIV-infected patients admitted to a public hospital in Phnom Penh, Cambodia between December 1999 and May 2000 was performed. The in-hospital mortality rate was 43.6%. Approximately 50% of patients had two or more concurrent illnesses. Very advanced HIV disease was common, with CD4 cell counts below 10 cells/mm(3) in 43.2%. Only 28.3% of the patients had documentation of their HIV infection prior to hospitalization. Chronic diarrhoea was the most frequent opportunistic illness (41.2%), followed by tuberculosis (26%), cryptococcal meningitis (12.6%), Pneumocystis carinii pneumonia (8.4%), and encephalitis (4.7%). Chronic diarrhoea and tuberculosis were the most important opportunistic infections observed in HIV-infected hospitalized patients in Cambodia. These findings illustrate the need for early diagnosis of HIV-infection, effective prophylaxis for opportunistic infections and improved access to antiretroviral therapy in Cambodia.

Directly observed therapy (DOT) for individuals with HIV: successes and challenges.

Many HIV-infected individuals have not reaped the benefits of combination antiretroviral therapy due to inability either to adhere to medications or to access care. It is now recognized that innovative approaches are needed to increase access and adherence to highly active antiretroviral therapy (HAART), especially among these hard-to-reach populations. Due to the success of directly observed therapy (DOT) for the treatment of Mycobacterium tuberculosis (TB), our group and others have questioned whether DOT can be adapted to deliver HAART to hard-to-reach communities. In this review, we discuss the results of pilot programs that have utilized DOT in multiple different settings and use case studies to explore the diverse issues that can arise when implementing these programs. As we continue to gain more experience with observed therapy, we will be able to better identify the key components for a successful intervention.

Clinical presentation and treatment of transfusion-associated babesiosis in premature infants.

We review here 7 cases of neonatal transfusion-associated babesiosis at a NICU in the northeast United States. Transfusion from 2 infected units of blood resulted in the 7 cases described. The clinical presentation was highly variable in this cohort; the extremely low birth weight neonates were the most severely affected. Antibiotic therapy was effective in neonates with mild and asymptomatic infection; however, double-volume exchange blood transfusion with prolonged multidrug treatment was required for the 2 most severe cases. The risk of Babesia microti infection is not eliminated through current blood-bank practices. Neonatologists in endemic areas should have a high index of suspicion for babesiosis in premature infants exposed to blood transfusions.

Patterns of sexual behaviour of male patients before testing HIV-positive in a Cambodian hospital, Phnom Penh.

BACKGROUND: Sexual behaviours among HIV-positive male patients in Cambodia have not been fully evaluated. OBJECTIVES: The patterns of sexual behaviours and social factors were compared between married and single men. METHODS: A retrospective cross-sectional survey of 174 male HIV patients was undertaken during March 1999-June 2000 in Phnom Penh. RESULTS: Many participants (61%) reported that they were unaware that their sexual behaviours may have put them at risk of HIV infection. Sexual behaviours included having sex with a sex worker (90%), multiple sexual partners (41%), and both of these behaviours (37%). Two-thirds (69%) reported using a condom when having sex with a sex worker. Condom use with multiple sexual partners was low (24%). A history of condom use with a sex worker was less likely to be reported among married men than single men (P = 0.008). Always using condoms with a sex worker did not differ between married men and single men. Social factors that influenced visiting a sex worker included invitation by a friend (88%), alcohol consumption (74%), and having extra spending money (72%). Multivariate analysis suggests that alcohol consumption (P = 0.008) and having extra spending money (P = 0.02) were strongly associated with visiting a sex worker. CONCLUSIONS: In Cambodia, HIV-infected men frequently reported a history of using sex workers. Having multiple sex partners or using a sex worker and multiple sexual partners were not rare. Interventions should target men in settings where alcohol is consumed and to encourage married men to use condoms.