Predictors of Toxoplasma gondii IgG Seropositivity and Cranial Ultrasound Patterns among Children with Hydrocephalus.

BACKGROUND: Toxoplasma gondii infection during pregnancy is associated with serious neonatal complications, including hydrocephalus. In many high-income countries, T. gondii screening and treatment during the antenatal period are routinely carried out to prevent associated complications, whereas in most low-income countries, there is no routine screening of T. gondii during pregnancy. Despite the parasite being common in Tanzania, there is a paucity of information on the prevalence of T. gondii and cranial ultrasound patterns among children with hydrocephalus. METHODS: An analytical cross-sectional hospital-based study involving 125 infants with hydrocephalus attending the Bugando Medical Centre (BMC) was conducted between May 2017 and February 2018. Sociodemographic and other relevant information was collected using a pretested data collection tool. Venous blood samples were collected, and sera were used for the detection of specific T. gondii antibodies by indirect enzyme-linked immunosorbent assay (ELISA) as per manufacturer's instructions. Data were analysed using STATA version 13 software. RESULTS: The mean age of enrolled children was 4.8 ± 3.5 months. Out of 125 infants with hydrocephalus, 29 (23.2%, 95% CI: 21-36) were seropositive for T. gondii-specific IgG antibodies. By multiple generalized linear model analysis, being male (aRR = 1.1, 95% CI: 0.9-1.5, p = 0.049), higher birth order (aRR = 1.2, 95% CI: 1.0-1.5, p = 0.023), consumption of fish meat (aRR = 1.6, 95% CI: 1.2-2.3, p = 0.003), and using other methods of cooking meat than boiling (aRR = 1.7, 95% CI: 1.1-2.5, p = 0.015) were independent risk factors for T. gondii IgG seropositivity. Obstructive hydrocephalus was significantly more common among T. gondii-seronegative infants compared to IgG-seropositive infants (31.3% [30/96] vs. 13.8% [4/29]; p = 0.049). CONCLUSIONS: A significant proportion of infants with nonobstructive hydrocephalus are T. gondii IgG seropositive, and this is predicted by male gender, increase of birth order, consuming fish, and using other methods of cooking meat than boiling. These facts highlight the importance of continuing health education for pregnant women regarding T. gondii transmission and the need to follow-up their infants so that appropriate counselling and management can be provided.

High Clostridium difficile Infection among HIV-Infected Children with Diarrhea in a Tertiary Hospital in Mwanza, Tanzania.

Clostridium difficile causes a million of illnesses each year worldwide and can affect people of all ages. Limited data exist on the prevalence of C. difficile infections (CDI) among children below five years of age in developing countries. This study is aimed at determining the prevalence, associated factors, and outcome of the Clostridium difficile infection among children with diarrhea attending a tertiary hospital in Mwanza, Tanzania. Stool samples were collected and cultured anaerobically to isolate Clostridium difficile, followed by C. difficile toxin A and B assay and ribotyping. A total of 301 children with diarrhea were enrolled. A total of 22 (7.31%, 95% CI: 0.89-0.95) nonrepetitive stool samples were positive for Clostridium difficile. Eighteen (81%) of C. difficile isolates were toxigenic, and 16 (72.7%) had unknown ribotypes. Independent predictors of positive C. difficile were as follows: positive HIV status, hospital stay of more than four days, high stool leukocyte count, and watery stool. Clostridium difficile-positive children had significantly higher median duration of the diarrhea than those without C. difficile. Clinicians should consider C. difficile as a possible cause of diarrhea in children living in developing countries and institute appropriate management to prevent associated morbidities and mortalities. Furthermore, there is a need of joint effort to improve C. difficile diagnosis and surveillance in developing countries to establish the unknown epidemiology of CDI in these countries.

Prevalence and factors associated with renal dysfunction in children admitted to two hospitals in northwestern Tanzania.

BACKGROUND: It is evident that renal dysfunction (RD) is associated with unique infectious and non-infectious causes in African children. However, little data exists about the prevalence and factors associated with RD in children admitted to African hospitals. METHODS: In this cross-sectional study, we enrolled all children admitted to pediatric wards of Bugando Medical Centre (BMC) and Sekou-Toure Regional Referral hospital (SRRH) during a 6 month time period. Socio-demographical, clinical and laboratory data were collected using a structured questionnaire. Estimated glomerular filtration rate (eGFR) was calculated using modified Schwartz equation and those with < 60 ml/min/1.73m2were considered to have RD. Data analysis was done using STATA version 13 and considered significant when p-value was < 0.05. RESULTS: A total of 513 children were enrolled, of which 297 (57.9%) were males. Median age of children with and without RD was 34 months (27-60) and 46.5 (29-72) respectively. Prevalence of RD was 16.2%. Factors associated with RD were herbal medication use (p = 0.007), history of sore throat or skin infection (p = 0.024), sickle cell disease (SCD) (p = 0.006), dehydration (p = 0.001), malaria (p = 0.01) and proteinuria (p = < 0.001). CONCLUSIONS: High prevalence of RD was observed among children admitted to referral hospitals in Mwanza. Screening for RD should be performed on admitted children, particularly those with history of herbal medication use, sore throat/skin infection, SCD, dehydration and malaria. Where creatinine measurement is not possible, screening for proteinuria is a reasonable alternative.

Tuberculosis Contact Screening and Isoniazid Preventive Therapy Among Children Under 5 in the Mbeya and Songwe Regions, Tanzania.

INTRODUCTION: The World Health Organization (WHO) recommends contact screening and initiation of isoniazid preventive therapy (IPT) for children under 5 years of age exposed to a sputum smear-positive (SS+) tuberculosis (TB) source case. We conducted this study in order to assess implementation of these recommendations in southwestern Tanzania. METHODS: We conducted this cross-sectional study from June to August 2015 in 12 selected health facilities in the Mbeya and Songwe regions of Tanzania. Adult SS+ pulmonary TB patients living in the same household as children under 5 were enrolled. Structured questionnaires were used to obtain sociodemographic information and details about screening and intervention activity related to contact children under 5. Data were analysed using Stata version 11.0. RESULTS: We enrolled 257 index cases, who collectively had 433 contact children under 5. The median age of the index cases was 34 years (interquartile range 28 to 41) and 52.9% were male. Out of 433 contacts, 31 (7.2%) were screened for TB, of whom 7 (22.6%) were treated for presumptive TB. Among those screened, 24 were not diagnosed with TB, of whom only 8 (33.3%) received IPT. CONCLUSION: Low uptake of TB contact screening and IPT administration among eligible children under 5 was observed in this study. Health-care workers should be sensitized to screening of household contacts of adults with SS+ TB and initiate IPT in those who are eligible.

High birth prevalence of sickle cell disease in Northwestern Tanzania.

BACKGROUND: Worldwide, hemoglobinopathies affect millions of children. Identification of hemoglobin disorders in most sub-Saharan African countries is delayed until clinical signs of the disease are present. Limited studies have been conducted to understand their prevalence and clinical presentation among newborns in resource-limited settings. METHODOLOGY: This was a prospective cohort study. Newborns (aged 0-7 days) at two hospitals in Northwestern Tanzania were enrolled and followed prospectively for 6 months. Clinical and laboratory information were collected at baseline. Participants were screened for hemoglobinopathies using high-performance liquid chromatography. Clinical and laboratory follow-up was performed at 3 and 6 months for those with hemoglobinopathies as well as a comparison group of participants without hemoglobinopathies. RESULTS: A total of 919 newborns were enrolled. Among these, 1.4% (13/919) had sickle cell anemia or Hb S/ß0 -thalassemia (Hb FS), and 19.7% (181/919) had sickle cell trait or Hb S/ß+ thalassemia (Hb FAS). Furthermore, 0.2% (two of 919) had ß+ -thalassemia. Red cell indices compared between Hb FS, Hb FAS, and Hb FA were similar at baseline, but hemoglobin was lower and red cell distribution width was higher in children with Hb FS at 3- and 6-month follow-up. Febrile episodes were more common for children with Hb FS at 3- and 6-month follow-up. CONCLUSION: The prevalence of sickle cell disease among neonates born in Northwestern Tanzania is one of the highest in the world. Newborn screening is needed early in life to identify neonates with hemoglobinopathies so that clinical management may commence and morbidity and mortality related to hemoglobinopathies be reduced.

Reversible Severe Pulmonary Hypertension after Adenotonsillectomy: A Case Report of a Child Treated at Bugando Medical Centre, Northwestern Tanzania.

Upper airway obstruction (UAO) due to adenotonsillar hypertrophy represents one of the rare causes of pulmonary hypertension in children. We report a case of adenotonsillar hypertrophy, managed at pediatric and otorhinolaryngology departments in Bugando Medical Centre (BMC), northwestern Tanzania, with complete remission of symptoms of pulmonary hypertension following adenotonsillectomy. A 17-month-old boy presented with difficulty breathing, dry cough, and noisy breathing since 1 year. He had facial and lower limb oedema with a pan systolic murmur at the tricuspid area, fine crepitations, and tender hepatomegaly. A grade II tonsillar hypertrophy and hypertrophied adenoids were seen on nasal and throat evaluation. A 2D-echocardiography showed grossly distended right atrium and ventricle, dilated pulmonary artery, and grade III tricuspid regurgitation. His final diagnosis was severe pulmonary hypertension with right-sided heart failure due to adenotonsillar hypertrophy. He had complete remission of cardiopulmonary symptoms after adenotonsillectomy and had normal control echocardiography six and twelve months after surgery. Children with symptoms of upper airway obstruction and cardiopulmonary involvement could benefit from routine screening for pulmonary hypertension. Adenotonsillectomy should be considered for possible complete remission of both UAO and cardiopulmonary symptoms.

Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial.

BACKGROUND: HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients. METHODS: Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/µl, the absence of AIDS-defining symptoms and an ART-naïve therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/µl. RESULTS: No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 ± 5.70 cells/µl compared to -37.42 ± 10.77 cells/µl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men. CONCLUSIONS: This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT01299948.

Relationship between non-Hodgkin's lymphoma and blood levels of Epstein-Barr virus in children in north-western Tanzania: a case control study.

BACKGROUND: Non-Hodgkin's Lymphomas (NHL) are common in African children, with endemic Burkitt's lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania. METHODS: A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 - 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024). CONCLUSIONS: BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children.