Alexander J Stockdale

Liver Fibrosis by Transient Elastography and Virologic Outcomes After Introduction of Tenofovir in Lamivudine-Experienced Adults With HIV and Hepatitis B Virus Coinfection in Ghana

BACKGROUND Antiretroviral treatment (ART) programs in sub-Saharan Africa have for many years included lamivudine as the sole hepatitis B virus (HBV) inhibitor. Long-term outcomes and the effects of introducing tenofovir as part of ART in these populations have not been characterized. METHODS The study comprised a cross-sectional analysis of 106 human immunodeficiency virus (HIV)/HBV-coinfected subjects maintained on lamivudine, as well as a prospective analysis of 76 lamivudine-experienced subjects who introduced tenofovir. Patients underwent assessment of liver fibrosis by transient elastography (TE) and testing to characterize HIV type 1 (HIV-1) and HBV replication. RESULTS After a median of 45 months of lamivudine treatment, HIV-1 RNA and HBV DNA were detectable in 35 of 106 (33.0%) and 54 of 106 (50.9%) subjects, respectively, with corresponding drug resistance rates of 17 of 106 (16.0%) and 31 of 106 (29.2%), respectively. Median TE values were 5.7 kPa (interquartile range, 4.7-7.2 kPa) and independently associated with HBV DNA load, aspartate aminotransferase levels, and platelet counts; 13 of 106 (12.3%) subjects had TE measurements >9.4 kPa. Twelve months after the first assessment, and a median of 7.8 months after introducing tenofovir, HBV DNA levels declined by a mean of 1.5 log10 IU/mL (P < .001). TE values changed by a mean of -0.2 kPa (P = .097), and declined significantly in subjects who had pretenofovir HBV DNA levels >2000 IU/mL (mean, -0.8 kPa; P = .048) or TE values >7.6 kPa (mean, -1.2 kPa; P = .021). HIV-1 RNA detection rates remained unchanged. CONCLUSIONS A proportion of HIV/HBV-coinfected patients on long-term lamivudine-containing ART had poor HIV and HBV suppression, drug resistance, and TE values indicative of advanced liver fibrosis. Tenofovir improved HBV control and reduced liver stiffness in subjects with high HBV DNA load and TE values.

Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis

Summary Background Hepatitis D virus (also known as hepatitis delta virus) can establish a persistent infection in people with chronic hepatitis B, leading to accelerated progression of liver disease. In sub-Saharan Africa, where HBsAg prevalence is higher than 8%, hepatitis D virus might represent an important additive cause of chronic liver disease. We aimed to establish the prevalence of hepatitis D virus among HBsAg-positive populations in sub-Saharan Africa. Methods We systematically reviewed studies of hepatitis D virus prevalence among HBsAg-positive populations in sub-Saharan Africa. We searched PubMed, Embase, and Scopus for papers published between Jan 1, 1995, and Aug 30, 2016, in which patient selection criteria and geographical setting were described. Search strings included sub-Saharan Africa, the countries therein, and permutations of hepatitis D virus. Cohort data were also added from HIV-positive populations in Malawi and Ghana. Populations undergoing assessment in liver disease clinics and those sampled from other populations (defined as general populations) were analysed. We did a meta-analysis with a DerSimonian-Laird random-effects model to calculate a pooled estimate of hepatitis D virus seroprevalence. Findings Of 374 studies identified by our search, 30 were included in our study, only eight of which included detection of hepatitis D virus RNA among anti-hepatitis D virus seropositive participants. In west Africa, the pooled seroprevalence of hepatitis D virus was 7·33% (95% CI 3·55–12·20) in general populations and 9·57% (2·31–20·43) in liver-disease populations. In central Africa, seroprevalence was 25·64% (12·09–42·00) in general populations and 37·77% (12·13–67·54) in liver-disease populations. In east and southern Africa, seroprevalence was 0·05% (0·00–1·78) in general populations. The odds ratio for anti-hepatitis D virus detection among HBsAg-positive patients with liver fibrosis or hepatocellular carcinoma was 5·24 (95% CI 2·74–10·01; p<0·0001) relative to asymptomatic controls. Interpretation Findings suggest localised clusters of hepatitis D virus endemicity across sub-Saharan Africa. Epidemiological data are needed from southern and east Africa, and from patients with established liver disease. Further studies should aim to define the reliability of hepatitis D virus testing methods, identify risk factors for transmission, and characterise the natural history of the infection in the region. Funding Wellcome Trust, Royal Society.

An audit of acute bacterial meningitis in a large teaching hospital 2005–10

BACKGROUND Acute bacterial meningitis (ABM) is a rare disease associated with severe neurological sequelae and death. Clinical features on admission may be subtle and thus delay recognition. Previous studies have shown association between early administration of antibiotics and favourable outcomes. AIM To examine the presenting clinical features of patients aged >15 years with ABM admitted to a University teaching hospital. To audit investigations and treatment including lumbar puncture (LP), computed tomography (CT) and antibiotics against British Infection Association guidelines. DESIGN Retrospective observational audit. METHODS Hospital records were reviewed for presenting clinical features and timing of CT scan, LP and antibiotics. RESULTS Records of 39 patients with ABM were reviewed. The classical triad of fever, neck stiffness and altered mental state was present on admission in only 21% of cases. LP was contraindicated in 69% of cases. Immediate LP was carried out in only 17% of those who had no contraindication. Antibiotics were administered after a median of 79 min (interquartile range 24-213 min); 65% were given within 3 h after arrival. Eighty-five percent of patients had antibiotics in accordance with local guidelines. CONCLUSION In patients with ABM, the classical clinical features are uncommon on arrival to hospital and frequently evolve following admission. The majority of patients have contraindications to immediate LP. Efforts should be made to facilitate immediate LP performed in the Emergency Department when there are no contraindications. Earlier administration of antibiotics in cases of suspected ABM and close review following admission is recommended.

Chronic hepatitis B infection in sub-Saharan Africa: a grave challenge and a great hope

In sub-Saharan Africa, chronic infection with the hepatitis B virus (HBV) is a profoundly important public health issue characterised by high prevalence, frequent co-infection with HIV, and suboptimally applied ascertainment and management strategies. Prevalence of hepatitis B surface antigen (HBsAg) in the general population varies geographically, with the highest rates (.8%)

Case Report : Severe Typhus Group Rickettsiosis Complicated by Pulmonary Edema in a Returning Traveler from Indonesia

We report a severe case of typhus group rickettsiosis in a returning traveler from Indonesia. This typically mild illness was characterized by progressive pulmonary edema and prolonged fever, with defervescence 4 days after the commencement of doxycycline.

Effectiveness of Protease Inhibitor/Nucleos(t)ide Reverse Transcriptase Inhibitor-Based Second-line Antiretroviral Therapy for the Treatment of Human Immunodeficiency Virus Type 1 Infection in Sub-Saharan Africa: A Systematic Review and Meta-analysis

In sub-Saharan Africa, second-line ritonavir-boosted protease inhibitor–based antiretroviral therapy led to virological suppression in 69.3% of participants at week 48 and 61.5% at week 96, based on an intention-to-treat meta-analysis of 4558 participants (14 studies) and 2145 participants (8 studies), respectively.

Evaluation of HIV testing recommendations in specialty guidelines for the management of HIV indicator conditions.

European guidelines recommend HIV testing for individuals presenting with indicator conditions (ICs) including AIDS‐defining conditions (ADCs). The extent to which non‐HIV specialty guidelines recommend HIV testing in ICs and ADCs is unknown. Our aim was to pilot a methodology in the UK to review specialty guidelines and ascertain if HIV was discussed and testing recommended.

Initiation of antiretroviral therapy in HIV‐infected tuberculosis patients in rural Kenya: an observational study

To provide information on the effect of timing of antiretroviral therapy (ART) initiation on outcomes of TB infection in real‐life, non‐clinical trial, rural settings in sub‐Saharan Africa.

Effectiveness of protease inhibitor/nucleos(t)ide reverse transcriptase inhibitor-based second-line antiretroviral therapy for the treatment of HIV-1 infection in sub-Saharan Africa: systematic review and meta-analysis.

In sub-Saharan Africa, second-line ritonavir-boosted protease inhibitor–based antiretroviral therapy led to virological suppression in 69.3% of participants at week 48 and 61.5% at week 96, based on an intention-to-treat meta-analysis of 4558 participants (14 studies) and 2145 participants (8 studies), respectively.

A Granulomatous Chronic Disease

A 27-year-old man presented with a 3-week history of fever, night sweats, and right upper quadrant pain. He had a childhood diagnosis of Crohn’s disease requiring resection of the rectosigmoid colon, with colostomy formation when he was 13 years old. Histology revealed deep fissuring of the mucosa with extension into the muscularis propria, multiple granulomata, increased inflammatory cells including eosinophils within the lamina propria, and some irregularity of the mucosa with distortion of glands. He described recurrent axillary and skin abscesses for several years. Two years before presentation, he was admitted with septic shock, and a large intrahepatic abscess was identified on computed tomography (CT). Ultrasound guided drainage of this cultured Staphylococcus aureus and he was treated with 1 month of intravenous and 8 weeks of oral flucloxacillin. At 2 months, there was a small residual collection visible on CT. On examination, his abdomen was tender in the right upper quadrant and he was febrile at 39.0 C. Liver enzymes were moderately elevated, showing an obstructive picture. C-reactive protein was elevated at 286 mg/L (normal 0-5), white cell count 12.1 10/L, neutrophil count 9.80 10/L, lymphocyte count 1.34 10/L, and platelets 418 10/L. Blood cultures were negative, and human immunodeficiency virus serology was negative. An abdominal CT scan demonstrated a recurrent low attenuation mass in the posterior right lobe of the liver, measuring 10 cm in diameter with mixed solid and fluid components (Figure 1). Pus was aspirated under ultrasound guidance, again growing Staphylococcus aureus. It was noted during this procedure that the aspiration was difficult due to the organized nature of the collection. In view of the childhood colitis, the history of skin abscesses, and in particular, the recurring and organized nature of the staphylococcal liver abscess, we suspected an immunodeficiency. A neutrophil function test was therefore arranged, which demonstrated impaired production