1.5 Tesla Magnetic Resonance Imaging to Investigate Potential Etiologies of Brain Swelling in Pediatric Cerebral Malaria.

The hallmark of pediatric cerebral malaria (CM) is sequestration of parasitized red blood cells in the cerebral microvasculature. Malawi-based research using 0.35 Tesla (T) magnetic resonance imaging (MRI) established that severe brain swelling is associated with fatal CM, but swelling etiology remains unclear. Autopsy and clinical studies suggest several potential etiologies, but limitations of 0.35 T MRI precluded optimal investigations into swelling pathophysiology. A 1.5 T MRI in Zambia allowed for further investigations including susceptibility-weighted imaging (SWI). SWI is an ideal sequence for identifying regions of sequestration and microhemorrhages given the ferromagnetic properties of hemozoin and blood. Using 1.5 T MRI, Zambian children with retinopathy-confirmed CM underwent imaging with SWI, T2, T1 pre- and post-gadolinium, diffusion-weighted imaging (DWI) with apparent diffusion coefficients and T2/fluid attenuated inversion recovery sequences. Sixteen children including two with moderate/severe edema were imaged; all survived. Gadolinium extravasation was not seen. DWI abnormalities spared the gray matter suggesting vasogenic edema with viable tissue rather than cytotoxic edema. SWI findings consistent with microhemorrhages and parasite sequestration co-occurred in white matter regions where DWI changes consistent with vascular congestion were seen. Imaging findings consistent with posterior reversible encephalopathy syndrome were seen in children who subsequently had a rapid clinical recovery. High field MRI indicates that vascular congestion associated with parasite sequestration, local inflammation from microhemorrhages and autoregulatory dysfunction likely contribute to brain swelling in CM. No gross radiological blood brain barrier breakdown or focal cortical DWI abnormalities were evident in these children with nonfatal CM.

Burden of respiratory tract infections at post mortem in Zambian children.

BACKGROUND: Autopsy studies are the gold standard for determining cause-of-death and can inform on improved diagnostic strategies and algorithms to improve patient care. We conducted a cross-sectional observational autopsy study to describe the burden of respiratory tract infections in inpatient children who died at the University Teaching Hospital in Lusaka, Zambia. METHODS: Gross pathology was recorded and lung tissue was analysed by histopathology and molecular diagnostics. Recruitment bias was estimated by comparing recruited and non-recruited cases. RESULTS: Of 121 children autopsied, 64 % were male, median age was 19 months (IQR, 12-45 months). HIV status was available for 97 children, of whom 34 % were HIV infected. Lung pathology was observed in 92 % of cases. Bacterial bronchopneumonia was the most common pathology (50 %) undiagnosed ante-mortem in 69 % of cases. Other pathologies included interstitial pneumonitis (17 %), tuberculosis (TB; 8 %), cytomegalovirus pneumonia (7 %) and pneumocystis Jirovecii pneumonia (5 %). Comorbidity between lung pathology and other communicable and non-communicable diseases was observed in 80 % of cases. Lung tissue from 70 % of TB cases was positive for Mycobacterium tuberculosis by molecular diagnostic tests. A total of 80 % of TB cases were comorbid with malnutrition and only 10 % of TB cases were on anti-TB therapy when they died. CONCLUSIONS: More proactive testing for bacterial pneumonia and TB in paediatric inpatient settings is needed.

High rates of congenital cytomegalovirus infection linked with maternal HIV infection among neonatal admissions at a large referral center in sub-Saharan Africa.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the major infectious cause of birth defects and hearing loss globally. There is a growing recognition of the potential clinical impact of congenital CMV infections in high-seroprevalence settings. METHODS: A cross-sectional study of neonatal admissions at a large referral center in sub-Saharan Africa to determine the prevalence of both symptomatic and asymptomatic congenital CMV infection was performed. Real-time polymerase chain reaction was used to screen DNA-extracted sera, urine, and saliva, and an enzyme-linked immunosorbent assay was used to screen serum samples for anti-CMV immunoglobulin M. Multivariate binary logistic regression was used to identify risk factors associated with increased odds of congenital CMV infection. RESULTS: Congenital CMV was detected in 3.8% (15/395) of neonates. Among these infants, 6 of 15 (40%) presented with jaundice, 1 of whom also had petechiae. Congenital CMV infection was detected in 9 of 79 (11.4%; 95% confidence interval [CI], 6.1%-20.3%) neonates born to human immunodeficiency virus (HIV)-infected mothers, and both maternal HIV (odds ratio [OR], 6.661 [95% CI, 2.126-20.876], P = .001) and jaundice (OR, 5.701 [95% CI, 1.776-18.306], P = .003) were independently linked with significantly increased odds of congenital CMV infection. CONCLUSIONS: Congenital and early infant CMV infections may have important consequences for child health in sub-Saharan Africa and other high HIV and CMV seroprevalence populations globally.

Use of the Xpert(®) MTB/RIF assay for diagnosing pulmonary tuberculosis comorbidity and multidrug-resistant TB in obstetrics and gynaecology inpatient wards at the University Teaching Hospital, Lusaka, Zambia.

OBJECTIVES: In high-tuberculosis (TB)-endemic countries, comorbidity of pulmonary TB in hospitalised patients with non-communicable diseases is well documented. In this study, we evaluated the use of the Xpert(®) MTB/RIF assay for the detection of concomitant pulmonary TB in patients admitted to the University Teaching Hospital, Lusaka, Zambia, with a primary obstetric or gynaecological condition. METHODS: The Study population were inpatients admitted with a primary obstetric or gynaecological problem who had a concomitant cough and were able to expectorate a sputum sample. Sputum samples from 94 patients were analysed for the presence of Mycobacterium tuberculosis (M.tb) by standard smear microscopy, MGIT culture, MGIT drug-susceptibility testing (DST) and the Xpert(®) MTB/RIF assay. The sensitivity and specificity of the Xpert(®) MTB/RIF assay were evaluated against the culture gold standard. RESULTS: Twenty-six of 94 (27.7%) patients had culture-confirmed pulmonary TB. The Xpert(®) MTB/RIF assay had a sensitivity of 80.8% [95% CI: 60.0-92.7%]) compared against MGIT culture. The Xpert(®) MTB/RIF assay was more sensitive than sputum smear microscopy (21/26 (80.8%) vs. 13/26 (50.0%), P = 0.02) and detected an additional eight culture-confirmed cases. Culture DST analysis identified two monoresistant M.tb strains: one resistant to rifampicin (rifampicin sensitive by the Xpert(®) MTB/RIF assay) and one to ethambutol. HIV infection was linked with a 3-fold increase in risk of TB, accounting for 87.5% (21/24) of TB cases. 50% of cases presented as comorbidities with other communicable diseases (CDs) and non-communicable diseases (NCDs). CONCLUSIONS: As an alternative to sputum microscopy, the Xpert(®) MTB/RIF assay provides a sensitive, specific and rapid method for the diagnosis of pulmonary TB in obstetric or gynaecological inpatients. Pulmonary TB is an important cause of concomitant comorbidity to the obstetric or gynaecological condition necessitating admission. TB and HIV comorbidities with other communicable and non-communicable diseases were also common. More proactive screening for TB comorbidity is required in obstetric and gynaecological wards.

Neuropsychiatric and socioeconomic status impact antiretroviral adherence and mortality in rural Zambia.

We conducted a prospective cohort study of 496 adults starting antiretroviral treatment (ART) to determine the impact of neuropsychiatric symptoms and socioeconomic status on adherence and mortality. Almost 60% had good adherence based upon pharmacy records. Poor adherence was associated with being divorced, poorer, food insecure, and less educated. Longer travel time to clinic, concealing one's human immunodeficiency virus (HIV) status, and experiencing side effects predicted poor adherence. Over a third of the patients had cognitive impairment and poorer cognitive function was also associated with poor adherence. During follow-up (mean 275 days), 20% died-usually within 90 days of starting ART. Neuropsychiatric symptoms, advanced HIV, peripheral neuropathy symptoms, food insecurity, and poverty were associated with death. Neuropsychiatric symptoms, advanced HIV, and poverty remained significant independent predictors of death in a multivariate model adjusting for other significant factors. Social, economic, cognitive, and psychiatric problems impact adherence and survival for people receiving ART in rural Zambia.

High prevalent and incident HIV-1 and herpes simplex virus 2 infection among male migrant and non-migrant sugar farm workers in Zambia.

BACKGROUND: More insight is needed regarding risk factors for prevalent and incident HIV-1 infection among male farm workers in Sub-Saharan Africa to control the HIV-1 epidemic. METHODS: Male farm workers were recruited from a sugar estate in Zambia to participate in a prospective cohort study. Questionnaire data were collected via interview, and testing was conducted for HIV-1, herpes simplex virus type 2 (HSV-2), and syphilis infection at baseline and follow-up between May 2006 and September 2007. RESULTS: Among 1062 workers enrolled, HIV-1 prevalence at baseline was 20.7%. Testing HSV-2 seropositive (adjusted odds ratio (AOR) 5.4, 95% CI 3.6 to 8.1), self-reported genital ulcers in the past year (AOR 2.8, 95% CI 1.9 to 4.2), and being widowed (AOR 3.7, 95% CI 2.0 to 6.9) were significantly associated with prevalent HIV-1 infection. The HIV-1 incidence among 731 initially negative participants with at least one follow-up visit was 4.1 per 1000 person-months (95% CI 2.6 to 5.7); seroconversion was independently associated with prevalent HSV-2 infection (adjusted hazard ratio (AHR) 2.4, 95% CI 1.0 to 5.8) and incident HSV-2 infection (AHR 18.0, 95% CI 4.2 to 76.3). HIV-1 prevalence and incidence rates were similar among migrant and non-migrant workers. CONCLUSIONS: HIV-1 prevalence and incidence were high, and HSV-2 infection was a risk factor for HIV-1 acquisition. There is an urgent need to expand HIV-1 prevention programmes tailored to farm workers and their communities.