The significance of cytomegalovirus in children with pneumonia admitted for mechanical ventilation.

BACKGROUND: The pathogenic role of cytomegalovirus (CMV) among children with pneumonia is not clear. OBJECTIVES AND DESIGN: We describe the outcome of children on mechanical ventilation with 'probable' CMV-related pneumonitis (CMV DNA polymerase chain reaction [PCR] positive as well as clinical and imaging features of CMV on ganciclovir) and children with pneumonia and CMV infection (CMV DNA PCR-positive without clinical and imaging features of CMV and not on ganciclovir therapy) at a paediatric intensive care unit in South Africa between 2011 and 2013. CMV viral loads were measured in non-bronchoscopic bronchoalveolar lavage fluid (NBBALF), plasma and whole-blood samples. RESULTS: Of the 97 children enrolled, 38 had CMV-related pneumonitis, 27 had pneumonia and CMV infection and 32 had pneumonia without CMV infection (negative CMV DNA PCR). Survival in the three groups was respectively 73.7% (P < 0.05), 92.6% (P < 0.05) and 88.0%. The difference in outcome could be accounted for by variance in the prevalence of human immunodeficiency virus (HIV) infection (respectively 60.5% and 29.6%, P < 0.05). A higher CMV viral load in NBBALF and plasma was seen in cases of CMV-related pneumonitis than in pneumonia with CMV infection: respectively log 5.20 vs. log 4.10 (P < 0.05) and 4.56 vs. 3.47 (P < 0.05). CONCLUSIONS: HIV-infected children on mechanical ventilation with CMV-related pneumonitis on ganciclovir have poor outcomes. Randomised placebo-controlled studies on ganciclovir are required.

In vitro evaluation of metal chelators as potential metallo- ß -lactamase inhibitors.

AIMS: This study aimed at investigating the use of metal chelators as potential metallo-ß-lactamase inhibitors (MBL). METHODS AND RESULTS: The minimum inhibitory concentration (MIC) of meropenem was ascertained alone and in combination with various concentrations of macrocyclic (1,4,7- triazacyclononane-1-glutaric acid-4,7-diacetic acid = NODAGA) peptide derivatives and acyclic (N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine = TPEN and di-(2-picolyl)amine = DPA) metal chelators using the broth microdilution method. MICs of meropenem against carbapenem-resistant enterobacteriaceae (CRE) producing MBLs were decreased to concentrations as low as 0·06 mg l(-1) in the presence of some metal chelators. TPEN at 4 and 8 mg l(-1) showed the best activity by decreasing meropenem MICs to 0·5 and 0·06 mg l(-1) , respectively, for some New Delhi Metallo-beta-lactamase (NDM) and Verona integron-encoded metallo-ß-lactamase (VIM) -producing enterobacteriaceae. DPA at 8 and 16 mg l(-1) was also able to decrease meropenem MICs to 1 and 0·125 mg l(-1) , respectively, for these CREs. NODAGA peptide derivatives showed the least inhibition as 32 mg l(-1) was required for meropenem MICs to be decreased to 0·06 mg l(-1) against an NDM-1 producing isolate. CONCLUSION: The various metal chelators, TPEN, DPA and NODAGA peptide derivatives were able to inhibit the MBLs in decreasing order of activity, rendering CREs susceptible to meropenem. SIGNIFICANCE AND IMPACT OF THE STUDY: In the absence of new antibiotics, this study evaluated metal chelators as potential MBL inhibitors.

Hepatitis B and HIV co-infection in pregnant women: indication for routine antenatal hepatitis B virus screening in a high HIV prevalence setting.

BACKGROUND: Sub-Saharan Africa is endemic for hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections. HBV/HIV co-infection in women of reproductive age is of clinical and public health importance because these women constitute a significant reservoir for horizontal and perinatal HBV transmission. Childhood HBV vaccination from 6 weeks of age protects most children against chronic HBV infection. However, infants born to HBV/HIV co-infected women are more likely to be infected perinatally, with an increased risk of chronic hepatitis, than infants born to HBV mono-infected women. OBJECTIVES: The aim of our study was to establish the prevalence of HBV infection and HBV/HIV co-infection in pregnant women in KwaZulu-Natal, South Africa, to inform antenatal HBV screening and childhood immunisation policies in South Africa. METHODS: Stored plasma specimens obtained from 570 pregnant women were tested for hepatitis B surface antigen (HBsAg) and HBV infectivity, as characterised by the presence of hepatitis B e antigen (HBeAg) and/or HBV DNA load. RESULTS: The antenatal HIV prevalence and HBsAg prevalence in this study were 41.6% and 5.3% (95% confidence interval (CI) 3.4 - 7.1), respectively. Overall, 3.1% (95% CI 1.7 - 4.6) of pregnant women were HBV/HIV co-infected, with HBeAg positivity and the HBV DNA load being significantly higher in co-infected women. CONCLUSION: We report a 5.3% HBV prevalence and a 3.1% HBV/HIV co-infection prevalence in pregnant women from this HIV-endemic region. Routine antenatal HBV screening will allow early identification of neonates who require HBV active-passive immunoprophylaxis at birth. This strategy, together with antenatal antiretrovirals, will reduce the risk of perinatal HBV transmission, especially in high-risk HBV/ HIV co-infected pregnant women.

Resistance to antiretroviral drugs in newly diagnosed, young treatment-naïve HIV-positive pregnant women in the province of KwaZulu-Natal, South Africa.

In 2004, KwaZulu-Natal initiated one of the world's largest HIV/AIDS treatment programs. Studies in South Africa have shown that patients on antiretroviral therapy (ART) develop rapidly and transmit drug resistant mutations. Since resistance testing is not widely available in Kwazulu-Natal, the Department of Health conducted the first HIV drug resistance (HIVDR) threshold survey in 2005, which did not identify any mutations associated with HIVDR. The objective of this study was to conduct a follow-up threshold survey to update the information on HIVDR. This study was conducted in 2009 in five antenatal care sites in Kwazulu-Natal using the HIVDR threshold survey method developed by WHO. Two hundred and thirteen newly-diagnosed HIV positive, drug-naïve primigravidae, less than 22 years of age were included in the survey. Of the 82 HIV positive specimens, 17 had insufficient volume for genotyping and, of the remaining 65, 47 were genotyped sequentially. Drug resistance was identified by sequencing the HIV-1 pol gene, using the ViroSeq® HIV-1 genotyping system v2.0. Of the 47 samples that were genotyped, only one presented with a K103N mutation, which equates to a prevalence of transmitted HIVDR of <5%. The low prevalence of transmitted HIVDR is in keeping with statistical models of the early stages of ART rollout. As ART coverage is increasing continuously, there is a need to ensure that vigilance of HIVDR continues so that the emergence and spread of HIVDR is minimized.

Cerebellar abscess: the significance of cerebrospinal fluid diversion.

OBJECTIVE: Cerebellar abscesses that are often ominously silent have a significant mortality. Sudden total occlusion of cerebrospinal fluid (CSF) pathways makes an aggressive surgical approach mandatory. Our neurosurgical unit at Wentworth Hospital, Durban, South Africa, prospectively instituted a protocol for patients with cerebellar abscesses with reference to CSF diversion with the aim of improving outcome. Our 13-year experience with this approach to cerebellar abscesses is presented. METHODS: Since 1983, patients with cerebellar abscesses have been managed according to a standard protocol. In 1987, a policy of aggressive CSF diversion was prospectively instituted. This involved immediate CSF diversion in any patient with over or incipient hydrocephalus, even if fully conscious. The associated hydrocephalus was diagnosed on initial computed tomographic scans. CSF diversion was performed by means of a ventricular drain, inserted in the reception area under local anesthesia. The period from January 1983 to December 1995 was analyzed, and the impact of aggressive CSF diversion on patient outcome was evaluated. RESULTS: Seventy-seven patients with cerebellar abscesses during the 13-year period under review were studied. Thirty-four patients were treated before the introduction of the policy of aggressive CSF diversion. Of these patients, 10 died, resulting in a mortality of 29% and a morbidity of 21%. Forty-three patients were treated after the institution of the new policy of CSF diversion. Of these patients, five died, resulting in a mortality rate of 11.6% and a morbidity rate of 14%. CONCLUSION: Although surgical drainage of a cerebellar abscess and eradication of the primary septic source and appropriate antibiotic coverage are necessary, the management of hydrocephalus, or even incipient hydrocephalus, is of paramount importance.

Benefits to a regional neurosurgical unit following the introduction of a decentralised imaging facility.

OBJECTIVE: To determine whether the establishment of a peripheral computed tomography (CT) facility has an influence on the central referral neurosurgical unit, and particularly whether unnecessary referrals are avoided. DESIGN: The outpatient records of all patients referred from Umtata General Hospital (UGH) to the neurosurgical unit at Wentworth Hospital, Durban, were retrospectively analysed over a 4-year period--2 years before and 2 after the introduction of CT facilities at UGH. SETTING: Wentworth Hospital, Durban, which houses the sole neurosurgical referral centre for the region. PATIENTS: Eight hundred and forty patients were referred to the neurosurgical unit from UGH during the 4-year study period--July 1990 to June 1994. MAIN OUTCOME MEASURES: 1. The number of referrals to the neurosurgical unit before and after introduction of peripheral CT facilities at UGH. 2. The admission rate of the above referrals during the same periods, indicating appropriate referrals. RESULTS: 1. There were 536 patients referred from UGH to the neurosurgical unit over a 2-year period before the introduction of peripheral CT facilities, and 304 patients during the subsequent 2-year period after introduction of CT facilities at UGH. This represented a 43.3% decrease in patient referrals during a period in which referrals from all other areas increased by 2.6%. 2. The admission rate of patients (indicating appropriate referrals) being referred from UGH increased from 46.3% before CT facilities to 79.9% after the introduction of peripheral CT facilities. The admission rate of patients from other areas, excluding UGH, during the same periods, decreased from 50.3% to 46.4%. CONCLUSION: This audit reveals that following the introduction of CT facilities at UGH, the number of referrals to Wentworth Hospital's neurosurgical unit decreased by almost half (43.3%). Furthermore, the patients referred after introduction of the peripheral CT facility were more likely to be appropriate referrals (79.9%) than before (46.4%). Therefore, the provision of CT facilities at peripheral hospitals may effectively serve to exclude those patients who would otherwise be referred unnecessarily, and enable earlier referral of those patients who require urgent care at a tertiary neurosurgical unit.