Seasonality of childhood tuberculosis cases in Kampala, Uganda, 2010-2015.

BackgroundSeasonality in tuberculosis (TB) has been described, especially in children. However, few studies have assessed seasonality of TB in the equatorial region, and none in children.ObjectivesTo assess for seasonality of childhood TB cases in Kampala, Uganda, and determine the role of temperature, rainfall patterns, and influenza cases on TB diagnoses.MethodsWe retrospectively analyzed demographic and clinical data of children (under 15 years) diagnosed with TB at a pediatric TB clinic in Kampala, Uganda from 2010 to 2015. We performed decomposition analysis of the monthly case time series to assess seasonality. We compared monthly mean plots and performed Poisson regression to assess any association between TB diagnoses and temperature, rainfall, and influenza.ResultsOf the 713 childhood TB cases diagnosed at the clinic, 609 (85%) were clinically diagnosed and 492 (69%) were pulmonary cases. There were minimal monthly variations in TB cases, with a trough in December and peaks in July and October, but there was no significant seasonality. Temperature variations did not show a clear pattern with TB diagnoses. Rainfall alternated with TB diagnoses in the first half of the year, but then overlapped in the second half and was significantly associated with TB diagnoses. Influenza cases were significantly related to TB diagnoses with (β = 0.05, 95% CI 0.01 to 0.09, p = 0.01) or without (β = 0.06, 95% CI 0.01 to 0.1, p = 0.01) rainfall, and had particular overlap with pulmonary TB cases.ConclusionsSeasonal variations in childhood TB diagnoses were non-significant. Temperature did not have a clear pattern with TB diagnoses, but rainfall and influenza cases correlated with the primarily clinically diagnosed childhood TB cases

Prevalence of asthma among school children in Gaborone, Botswana.

Background: Asthma prevalence is high (>10%) in developed countries and although data is still missing for most of Africa, rates are increasing in developing regions as they become more westernized. We investigated the prevalence of asthma in school children in Gaborone, Botswana. Methods: This was a cross sectional descriptive study. ISAAC methodology was used. A representative proportionate size random sample of two age groups of children (13-14 year olds and 6-7 year olds) was consecutively enrolled from 10 schools. The schools were selected using a table of random numbers. A minimum sample size of 924 individuals (462 from each group) was adequate to achieve a precision of 3 % around our estimated prevalence of asthma of 10% with 95% confidence assuming a non-response rate of 20%. Data was collected using the validated International study of Asthma and Allergies in children (ISAAC) questionnaire. In accordance with the ISAAC criteria, Asthma was defined as wheezing in the previous 12 months. Data was captured in microsoft excel and analysed using SPSS version 23. Results: The prevalence of asthma (wheezing in the previous 12 months) was 16.5% (194/1175). Among the 6-7 year olds, the prevalence of asthma (wheezing in the previous 12 months) was 15.9%, while among the 13-14 years olds it was 16.8 %. The prevalence school type was 22.3 % in private schools versus 14.5 % in public schools. More severe asthma was associated with older children, 13 -14 years. The older children reported more limited speech due to wheezing (OR= 2.0, 95% CI =1.034, 3.9, p-value=0.043), ever had asthma (OR= 1.5, 95% CI=1.031, 2.3, p-value=0.034) and wheezing during exercise (OR=3.4, 95% CI= 2.5, 4.9, p-value= <0.001) compared to the younger children 6-7 years. Children from private schools had more wheezing symptoms. They were more likely to have ever wheezed (OR=2.2, .95% CI=1.7,2.9, p-value < 0.0001), wheezed in the previous twelve months (have asthma) (OR=1.7,95%CI=1.2,2.4, p-value = 0.001), ever had asthma (OR=2.4, 95% CI=1.7,3.5, pvalue< 0.0001), and wheezed during exercise (OR=1.8, 95% CI=1.4,2.4, p-value < 0.0001). Conclusion: The prevalence of asthma amongst school children in Gaborone, Botswana is high with older children experiencing more severe symptoms of asthma

Defeating Paediatric Tuberculous Meningitis: Applying the WHO "Defeating Meningitis by 2030: Global Roadmap".

Children affected by tuberculous meningitis (TBM), as well as their families, have needs that lie at the intersections between the tuberculosis and meningitis clinical, research, and policy spheres. There is therefore a substantial risk that these needs are not fully met by either programme. In this narrative review article, we use the World Health Organization (WHO) "Defeating Meningitis by 2030: global roadmap" as a starting point to consider key goals and activities to specifically defeat TBM in children. We apply the five pillars outlined in the roadmap to describe how this approach can be adapted to serve children affected by TBM. The pillars are (i) prevention; (ii) diagnosis and treatment; (iii) surveillance; (iv) support and care for people affected by meningitis; and (v) advocacy and engagement. We conclude by calling for greater integration between meningitis and TB programmes at WHO and at national levels

Breastfeeding and the risk of rotavirus diarrhea in hospitalized infants in Uganda: a matched case control study

<p>Abstract</p> <p>Background</p> <p><it>Rotavirus </it>is responsible for over 25 million outpatient visits, over 2 million hospitalizations and 527,000 deaths annually, worldwide. It is estimated that breastfeeding in accordance with the World Health Organization recommendations would save 1.45 million children's lives each year in the developing countries. The few studies that examined the effect of breastfeeding on <it>rotavirus </it>diarrhea produced conflicting results. This study aimed to determine the effect of breastfeeding on <it>rotavirus </it>diarrhea among admitted infants in Uganda.</p> <p>Methods</p> <p>The study was conducted in the Pediatrics medical emergency unit of a National Referral hospital during a peak incidence time for rotavirus from February to April 2008. It was an age matched case-control study with a ratio of 1:1. We consecutively enrolled infants presenting at the study site during this period whose caretakers consented to participate in the study. A minimum sample size of 90 pairs was adequate with power of 80% to detect a 30% decrease in breastfeeding rate among the cases assuming a breastfeeding rate of 80% in the controls. The infants with <it>rotavirus </it>positive results were the "cases". We used the commercial enzyme immunoassay kit (DAKO IDEIA™ rotavirus EIA detection kit) to diagnose the cases. The "controls" were admitted children with no diarrhea. We compared the cases and controls for antecedent breastfeeding patterns.</p> <p>Results</p> <p>Ninety-one matched case-control age-matched pairs with an age caliper of one month were included in the analysis. Breastfeeding was not protective against rotavirus diarrhea (OR 1.08: 95% CI 0.52 - 2.25; p = 0.8) in the conditional logistic model.</p> <p>Conclusions</p> <p>Our study findings did not reveal breastfeeding as protective against <it>rotavirus </it>diarrhea in infants. This suggests searching for other complementary preventive methods such as rotavirus vaccination and zinc supplementation to reduce the problem of <it>rotavirus </it>diarrhea in infants irrespective of their feeding practices.</p

Prevalence and factors associated with traditional herbal medicine use among patients on highly active antiretroviral therapy in Uganda

<p>Abstract</p> <p>Background</p> <p>In Africa, herbal medicines are often used as primary treatment for Human immunodeficiency virus (HIV) related problems. Concurrent use of traditional herbal medicines (THM) with antiretroviral drugs (ARVs) is widespread among HIV infected patients. However, the extent of THM use is not known in most settings in Sub-Saharan Africa. This study aimed at determining the prevalence and factors associated with THM use among HIV infected patients on highly active antiretroviral therapy (HAART) attending The AIDS Support Organization (TASO) in Uganda. TASO is a non-governmental organization devoted to offering HIV/AIDS care and treatment services in the population.</p> <p>Methods</p> <p>This was a cross-sectional study carried out in two TASO treatment centres in Uganda among 401 randomly selected eligible participants. We included participants who were 18 years and above, were enrolled on HAART, and consented to participate in the study. Data was collected using an interviewer-administered semi-structured questionnaire. THM use referred to someone who had ever used or was currently using herbal medicine while on highly active antiretroviral therapy (HAART) by the time of the study. Data was captured in Epi-data version 3.1 and exported to STATA version 9.0 for analysis.</p> <p>Results</p> <p>The prevalence of THM use was 33.7%. Patients on HAART for < 4 years were more likely to use THM (OR = 5.98, 95% CI 1.13 - 31.73) as well as those who experienced HAART side effects (OR = 3.66, 95% CI: 1.15 - 11.68). Older patients (≥39 years) were less likely to use THM (OR = 0.26 95% CI: 0.08 - 0.83). Participants with HAART adherence levels > 95% were less likely to use THM (OR = 0.09, 95% CI 0.01 - 0.65).</p> <p>Conclusion</p> <p>The prevalence of THM use among participants on HAART was high. This raises clinical and pharmacological concerns that need attention by the health care service providers.</p

Accuracy of Xpert Ultra in Diagnosis of Pulmonary Tuberculosis among Children in Uganda: a Substudy from the SHINE Trial.

Childhood tuberculosis (TB) presents significant diagnostic challenges associated with paucibacillary disease and requires a more sensitive test. We evaluated the diagnostic accuracy of Xpert MTB/RIF Ultra (Ultra) compared to other microbiological tests using respiratory samples from Ugandan children in the SHINE trial. SHINE is a randomized trial evaluating shorter treatment in 1,204 children with minimal TB disease in Africa and India. Among 352 samples and one cervical lymph node fine needle aspirate, one sample was randomly selected per patient and tested with the Xpert MTB/RIF assay (Xpert) and with Lowenstein-Jensen medium (LJ) and liquid mycobacterial growth indicator tube (MGIT) cultures. We selected only uncontaminated stored sample pellets for Ultra testing. We estimated the sensitivity of Xpert and Ultra against culture and a composite microbiological reference standard (any positive result). Of 398 children, 353 (89%) had culture, Xpert, and Ultra results. The median age was 2.8 years (interquartile range [IQR], 1.3 to 5.3); 8.5% (30/353) were HIV infected, and 54.4% (192/353) were male. Of the 353, 31 (9%) were positive by LJ and/or MGIT culture, 36 (10%) by Ultra, and 16 (5%) by Xpert. Sensitivities (95% confidence intervals [CI]) were 58% (39 to 65% [18/31]) for Ultra and 45% (27 to 64% [14/31]) for Xpert against any culture-positive result, with false positives of <1% and 5.5% for Xpert and Ultra. Against a composite microbiological reference, sensitivities were 72% (58 to 84% [36/50]) for Ultra and 32% (20 to 47% [16/50]) for Xpert. However, there were 17 samples that were positive only with Ultra (majority trace). Among children screened for minimal TB in Uganda, Ultra has higher sensitivity than Xpert. This represents an important advance for a condition which has posed a diagnostic challenge for decades

Prevalence and factors associated with rotavirus infection among children admitted with acute diarrhea in Uganda

<p>Abstract</p> <p>Background</p> <p>Rotavirus remains the commonest cause of severe dehydrating diarrhea among children worldwide. Children in developing countries die more because of several factors including poorer access to hydration therapy and greater prevalence of malnutrition. Hitherto, the magnitude of rotavirus disease in Uganda has remained unknown. This study was therefore done to determine the prevalence and factors associated with rotavirus infection among children aged 3-59 months admitted with acute diarrhea to paediatric emergency ward of Mulago Hospital, Uganda</p> <p>Methods</p> <p>Three hundred and ninety children, aged between 3-59 months with acute diarrhoea were recruited. The clinical history, socio-demographic characteristics, physical examination findings and laboratory investigations were recorded. Stool samples were tested for rotavirus antigens using the DAKO IDEIA rotavirus EIA detection kit.</p> <p>Results</p> <p>The prevalence of rotavirus infection was 45.4%. On multivariate analysis rotavirus was significantly associated with a higher education (above secondary) level of the mother [OR 1.8; 95% CI 1.1-2.7]; dehydration [OR 1.8; 95% CI 1.1-3.0] and breastfeeding [OR 2.6; 95% CI 1.4-4.0]. Although age was significantly associated with rotavirus on bivariate analysis; this association disappeared on multivariate analysis. No significant association was found between rotavirus infection and nutritional status, HIV status and attendance of day care or school.</p> <p>Conclusions</p> <p>Rotavirus infection is highly prevalent among children with acute diarrhoea admitted to Mulago Hospital in Uganda.</p

Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization-Recommended Weight Band Doses and Formulations.

BACKGROUND: Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization-recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. METHODS: Children weighing 4.0-7.9, 8.0-11.9, 12.0-15.9, or 16.0-24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0-36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. RESULTS: In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4-6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1-45.1), 16.7 (9.2-25.9), 317 (263-399), and 9.5 (7.5-11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0-7.9-, 8-11.9-, and ≥25-kg weight bands, isoniazid in the 4.0-7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. CONCLUSIONS: Recommended weight band-based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization-recommended doses requires further evaluation

Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial

Background: Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. Methods/design: SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Discussion: Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smearnegative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020. Trial registration: International Standard Randomised Controlled Trials Number: ISRCTN63579542, 14 October 2014. Pan African Clinical Trials Registry Number: PACTR201505001141379, 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017