Risk factors of severe pneumonia among children aged 2-59 months in western Kenya: a case control study

Introduction Globally, pneumonia is the leading cause of death in children under the age of 5 years. In Kenya, it is the second leading cause of mortality, accounting for greater than 30,000 deaths in this age group annually. This study sought to identify risk factors for severe pneumonia in children under the age of five years. Methods We conducted a case control study. Cases were children aged 2 to59 months with severe pneumonia or very severe pneumonia and controls were those with non-severe pneumonia as defined by the integrated management of childhood illnesses classification. We administered structured questionnaires to mothers of participants to obtain data on socio-demographics, nutritional status and potential environmental risk factors. Data was analyzed using Epi Info; significance level was set at 0.05. Results We recruited 103 cases and 103 controls. The median age of cases was 14.0 (Range 3-58) months and of controls 14.0 (Range 2-54) months. Comorbidity (Odds Ratio = 3.8, Confidence Interval 1.4-10.6), delay in seeking treatment for three days or more (Odds Ratio = 2.3, Confidence Interval 1.2-4.2) and contact with upper respiratory tract infection (Odds Ratio = 2.7, Confidence Interval 1.1-6.5) were independent risk factors for severe pneumonia. Receiving antibiotics at home (Odds Ratio = 0.4, Confidence Interval 0.2-0.8) was protective. Conclusion Co-morbidity, contact with upper respiratory tract infection and delay in seeking treatment are risk factors for severe pneumonia. We recommend health education regarding appropriate health seeking and engaging community health workers in pneumonia prevention, control and treatment.Pan African Medical Journal 2012; 13:4

Timing and Determinants of Tuberculosis Treatment Interruption in Nairobi County, Kenya

Tuberculosis (TB) treatment is a key pillar in the management and control of TB. Service delivery within the treatment facilities plays an important role in ensuring treatment adherence by TB patients. A prospective cohort study involving 25 health facilities, 25 facility in-charge officers and 291 patients diagnosed as new sputum smear positive (SM+) between December 2014 and July 2015 was undertaken. The aim of the study was to estimate the median time to treatment interruption, associated factors and overall predictors of non-adherence to TB treatment. A total of 19 (6.5%) treatment interruptions were observed. The median time to default was 56 [95% CI, 36-105] days. Treatment in a non-public facility [AOR=0.210, 95% CI (0.046-0.952)] and facilities perceived to have adequate number of health care workers to offer Directly Observed Therapy (DOT) [AOR=0.195, 95% CI (0.068-0.56)] showed a lower odds of treatment interruption whereas attainment of secondary level education [AOR=5.28, 95% CI (1.18-23.59)] indicated a higher odds of treatment interruption. Non-clinical aspects of health care service delivery influence patient adherence to TB treatment. Health seeking behavior of groups considered to be high risk for treatment interruption should be incorporated into the design and delivery of TB treatment

Molecular Epidemiology of Mycobacterium tuberculosis Complex Strains in Urban and Slum Settings of Nairobi, Kenya

Kenya is a country with a high tuberculosis (TB) burden. However, knowledge on the genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains and their transmission dynamics is sparsely available. Hence, we used whole-genome sequencing (WGS) to depict the genetic diversity, molecular markers of drug resistance, and possible transmission clusters among MTBC strains in urban and slum settings of Nairobi. We analyzed 385 clinical MTBC isolates collected between 2010 and 2015 in combination with patients’ demographics. We showed that the MTBC population mainly comprises strains of four lineages (L1–L4). The two dominating lineages were L4 with 55.8% (n = 215) and L3 with 25.7% (n = 99) of all strains, respectively. Genome-based cluster analysis showed that 30.4% (117/385) of the strains were clustered using a ≤5 single-nucleotide polymorphism (SNP) threshold as a surrogate marker for direct patient-to-patient MTBC transmission. Moreover, 5.2% (20/385) of the strains were multidrug-resistant (MDR), and 50.0% (n = 10) were part of a genome-based cluster (i.e., direct MDR MTBC transmission). Notably, 30.0% (6/20) of the MDR strains were resistant to all first-line drugs and are part of one molecular cluster. Moreover, TB patients in urban living setting had 3.8 times the odds of being infected with a drug-resistant strain as compared to patients from slums (p-value = 0.002). Our results show that L4 strains are the main causative agent of TB in Nairobi and MDR strain transmission is an emerging concern in urban settings. This emphasizes the need for more focused infection control measures and contact tracing of patients with MDR TB to break the transmission chain

Protocol for a Randomized Control Trial for Tungiasis Treatment in Homa Bay County, Kenya: Dimeticone versus Sodium Carbonate

Tungiasis, a World Health Organization neglected tropical disease, is caused by the female sand flea. Most clinical trials for tungiasis use expensive or impractical drugs, which are difficult for residents to use. However, in western Kenya, communities successfully treat tungiasis with sodium carbonate. We hypothesise that the topical risk-difference of 5% sodium carbonate is no more than 10% non-inferior to dimeticone (NYDA®) for tungiasis treatment. This is a protocol for a non-inferiority study, which will be randomised and with an observer-blinded control. The study will have two arms: 5% sodium carbonate and NYDA®, one on each foot, and will take place at state primary schools in Homa Bay County, Kenya. Fleas identified among school children aged 8–14 years with sand-flea lesions will be enrolled in the study. For each participant, the viability of the embedded fleas, clinical signs including inflammation, and symptoms will be monitored for seven days after treatment. The proportion of dead fleas will be compared in the primary analysis. All adverse events will be monitored throughout the study period. We expect to identify the most effective treatment between sodium carbonate and NYDA® for tungiasis, which can be adopted in the community.</jats:p

Protocol for a Randomized Control Trial for Tungiasis Treatment in Homa Bay County, Kenya: Dimeticone versus Sodium Carbonate

Tungiasis, a World Health Organization neglected tropical disease, is caused by the female sand flea. Most clinical trials for tungiasis use expensive or impractical drugs, which are difficult for residents to use. However, in western Kenya, communities successfully treat tungiasis with sodium carbonate. We hypothesise that the topical risk-difference of 5% sodium carbonate is no more than 10% non-inferior to dimeticone (NYDA®) for tungiasis treatment. This is a protocol for a non-inferiority study, which will be randomised and with an observer-blinded control. The study will have two arms: 5% sodium carbonate and NYDA®, one on each foot, and will take place at state primary schools in Homa Bay County, Kenya. Fleas identified among school children aged 8–14 years with sand-flea lesions will be enrolled in the study. For each participant, the viability of the embedded fleas, clinical signs including inflammation, and symptoms will be monitored for seven days after treatment. The proportion of dead fleas will be compared in the primary analysis. All adverse events will be monitored throughout the study period. We expect to identify the most effective treatment between sodium carbonate and NYDA® for tungiasis, which can be adopted in the community

Effects on the QT Interval of a Gatifloxacin-Containing Regimen versus Standard Treatment of Pulmonary Tuberculosis.

The effects on ventricular repolarization-recorded on the electrocardiogram (ECG) as lengthening of the QT interval-of acute tuberculosis and those of standard and alternative antituberculosis regimens are underdocumented. A correction factor (QTc) is introduced to make the QT independent of the heart rate, translating into the slope of the regression line between QT and heart rate being close to zero. ECGs were performed predosing and 1 to 5 h postdosing (month 1, month 2, and end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampin and isoniazid for 6 months and pyrazinamide and ethambutol for 2 months; "control") or a test regimen with gatifloxacin, rifampin, and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized controlled trial conducted in five African countries. Drug levels were measured at steady state (month 1) in a subset of patients. We compared treatment effects on the QTc and modeled the effect of individual drugs' maximum concentrations of drug in serum (Cmax) on the Fridericia-corrected QT interval. A total of 1,686 patients were eligible for the correction factor analysis of QT at baseline (mean age, 30.7 years; 27% female). Median heart rate decreased from 96/min at baseline to 71/min at end of treatment, and body temperature decreased from 37.2 to 36.5°C. Pretreatment, the nonlinear model estimated the best correction factor at 0.4081 in between Bazett's (0.5) and Fridericia's (0.33) corrections. On treatment, Fridericia (QTcF) was the best correction factor. A total of 1,602 patients contributed to the analysis of QTcF by treatment arm. The peak QTcF value during follow-up was >480 ms for 21 patients (7 and 14 in the test and control arms, respectively) and >500 ms for 9 patients (5 and 4, respectively), corresponding to a risk difference of -0.9% (95% confidence interval [CI], -2.0% to 2.3%; P = 0.12) and 0.1% (95% CI, -0.6% to 0.9%; P = 0.75), respectively, between the test and control arms. One hundred six (6.6%) patients had a peak measurement change from baseline of >60 ms (adjusted between-arm difference, 0.8%; 95% CI, -1.4% to 3.1%; P = 0.47). No evidence was found of an association between Cmax of the antituberculosis drugs 1 month into treatment and the length of QTcF. Neither a standard 6-month nor a 4-month gatifloxacin-based regimen appears to carry a sizable risk of QT prolongation in patients with newly diagnosed pulmonary tuberculosis. This is to date the largest data set studying the effects of antituberculosis regimens on the QT, both for the standard regimen and for a fluoroquinolone-containing regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT00216385.)

Effects of Mega Dose Micronutrient Supplementation On Serum Zinc, Retinol and Immune Status of Adult Males and Females Diagnosed with and Without HIV, Malaria and TB in Western Kenya – An Unpublished Perspective as at The Year 2004

Background: The role of micronutrients in management of HIV/AIDS, malaria and TB remains poorly understood worldwide. Objectives: To assess differences in mega dose nutritional management between HIV-seronegative and seropositive adult males and females diagnosed with HIV at Voluntary Testing and Counseling Centers (VCT) in Western Kenya. Methods: This was a randomized controlled study in which 90 subjects were recruited on the basis of an HIV-seropositive result from a voluntary and counseling center (VCT) using rapid HIV test kits. They were evaluated at baseline and every 4 weeks for 3 months to establish their clinical, biochemical and immunological status. After 12 weeks, 74 clients were still in the study, 9 were lost to follow-up while 7 had died. Of the 74 who completed the study, confirmation of baseline HIV status by ELIZA revealed that 63 were HIV-seropositive while 11 were HIV-seronegative despite losing spouses to HIV/AIDS. Correlations between parameters at baseline, during and after intervention were determined; Spearman’s Rho Coefficients indicating the level of significance. Group means were used to compare continuous data while categorical data was compared using Chi-Square. Results: Significant reductions in the clinical manifestation of disease were noted in the cohort after intervention for 12 weeks. Despite the large and different micronutrient dosages used between the two study arms, the only difference by arm of intervention was in the serum vitamin E level at 4 weeks which was much higher in arm 1 than it was in arm 2 of the study (p = 0.005). This might have been occasioned by the significant repletion of zinc in both arms, probably because use of citric acid in both arms improved zinc up-take from the supplements, food and/or reserves enabling other nutrients to be appropriately restored in both arms, these supporting the decision to pool the study arms and compare differences by HIV-seronegative and seropositive, notwithstanding the small sample sizes recruited but which nonetheless were our study limitation. Independent of the intervention arms, reduction of viral load by more than 0.5 log10 copies/ml correlated with higher baseline optical densities of HIV antibodies (P = 0.016) and higher baseline viral loads (p = 0.0001). A lower optical density of HIV antibodies at baseline correlated with higher serum zinc levels at 12 weeks (p = 0.008) and a lower Body Mass Index (BMI) at baseline (p = 0.029). Independent of the arm of study, a significant increase in CD4 cells counts post intervention correlated with lower baseline viral loads (p = 0.010), lower baseline NK cell counts (p = 0.007

A four-month gatifloxacin-containing regimen for treating tuberculosis.

BACKGROUND: Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control. This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis. METHODS: We conducted a noninferiority, randomized, open-label, controlled trial involving patients 18 to 65 years of age with smear-positive, rifampin-sensitive, newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries. A standard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin (400 mg per day) was substituted for ethambutol during the intensive phase and was continued, along with rifampin and isoniazid, during the continuation phase. The primary efficacy end point was an unfavorable outcome (treatment failure, recurrence, or death or study dropout during treatment) measured 24 months after the end of treatment, with a noninferiority margin of 6 percentage points, adjusted for country. RESULTS: A total of 1836 patients were assigned to the 4-month regimen (experimental group) or the standard regimen (control group). Baseline characteristics were well balanced between the groups. At 24 months after the end of treatment, the adjusted difference in the risk of an unfavorable outcome (experimental group [21.0%] minus control group [17.2%]) in the modified intention-to-treat population (1356 patients) was 3.5 percentage points (95% confidence interval, -0.7 to 7.7). There was heterogeneity across countries (P=0.02 for interaction, with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal) and in baseline cavitary status (P=0.04 for interaction) and body-mass index (P=0.10 for interaction). The standard regimen, as compared with the 4-month regimen, was associated with a higher dropout rate during treatment (5.0% vs. 2.7%) and more treatment failures (2.4% vs. 1.7%) but fewer recurrences (7.1% vs. 14.6%). There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen. CONCLUSIONS: Noninferiority of the 4-month regimen to the standard regimen with respect to the primary efficacy end point was not shown. (Funded by the Special Program for Research and Training in Tropical Diseases and others; ClinicalTrials.gov number, NCT00216385.)