A Preliminary Assessment of Rotavirus Vaccine Effectiveness in Zambia

BACKGROUND: Diarrhea is the third leading cause of child death in Zambia. Up to one-third of diarrhea cases resulting in hospitalization and/or death are caused by vaccine-preventable rotavirus. In January 2012, Zambia initiated a pilot introduction of the Rotarix live, oral rotavirus vaccine in all public health facilities in Lusaka Province. METHODS: Between July 2012 and October 2013, we conducted a case-control study at 6 public sector sites to estimate rotavirus vaccine effectiveness (VE) in age-eligible children presenting with diarrhea. We computed the odds of having received at least 1 dose of Rotarix among children whose stool was positive for rotavirus antigen (cases) and children whose stool was negative (controls). We adjusted the resulting odds ratio (OR) for patient age, calendar month of presentation, and clinical site, and expressed VE as (1 - adjusted OR) × 100. RESULTS: A total of 91 rotavirus-positive cases and 298 rotavirus-negative controls who had under-5 card-confirmed vaccination status and were ≥6 months of age were included in the case-control analysis. Among rotavirus-positive children who were age-eligible to be vaccinated, 20% were hospitalized. Against rotavirus diarrhea of all severity, the adjusted 2-dose VE was 26% (95% confidence interval [CI], -30% to 58%) among children ≥6 months of age. VE against hospitalized children ≥6 months of age was 56% (95% CI, -34% to 86%). CONCLUSIONS: We observed a higher point estimate for VE against increased severity of illness compared with milder disease, but were not powered to detect a low level of VE against milder disease

Detection of drug resistant Mycobacterium tuberculosis by high-throughput sequencing of DNA isolated from acid fast bacilli smears

BACKGROUND: Drug susceptibility testing for Mycobacterium tuberculosis (MTB) is difficult to perform in resource-limited settings where Acid Fast Bacilli (AFB) smears are commonly used for disease diagnosis and monitoring. We developed a simple method for extraction of MTB DNA from AFB smears for sequencing-based detection of mutations associated with resistance to all first and several second-line anti-tuberculosis drugs. METHODS: We isolated MTB DNA by boiling smear content in a Chelex solution, followed by column purification. We sequenced PCR-amplified segments of the rpoB, katG, embB, gyrA, gyrB, rpsL, and rrs genes, the inhA, eis, and pncA promoters and the entire pncA gene. RESULTS: We tested our assay on 1,208 clinically obtained AFB smears from Ghana (n = 379), Kenya (n = 517), Uganda (n = 262), and Zambia (n = 50). Coverage depth varied by target and slide smear grade, ranging from 300X to 12000X on average. Coverage of ≥20X was obtained for all targets in 870 (72%) slides overall. Mono-resistance (5.9%), multi-drug resistance (1.8%), and poly-resistance (2.4%) mutation profiles were detected in 10% of slides overall, and in over 32% of retreatment and follow-up cases. CONCLUSION: This rapid AFB smear DNA-based method for determining drug resistance may be useful for the diagnosis and surveillance of drug-resistant tuberculosis

The bacterial skin microbiome in psoriatic arthritis, an unexplored link in pathogenesis: challenges and opportunities offered by recent technological advances.

The resident microbial community, harboured by humans in sites such as the skin and gastrointestinal tract, is enormous, representing a candidate environmental factor affecting susceptibility to complex diseases, where both genetic and environmental risk factors are important. The potential of microorganisms to influence the human immune system is considerable, given their ubiquity. The impact of the host-gene-microbe interaction on the maintenance of health and the development of disease has not yet been assessed robustly in chronic inflammatory conditions. PsA represents a model inflammatory disease to explore the role of the microbiome because skin involvement and overlap with IBD implicates both the skin and gastrointestinal tract as sources of microbial triggers for PsA. In parallel with genetic studies, characterization of the host microbiota may benefit our understanding of the microbial contribution to disease pathogenesis-knowledge that may eventually inform the development of novel therapeutics

Inflammatory arthritis in HIV positive patients: A practical guide

Background: Musculoskeletal manifestations of the human immunodeficiency virus (HIV) have been described since the outset of the global HIV epidemic. Articular syndromes that have been described in association with HIV include HIV-associated arthropathy, seronegative spondyloarthropathies (SPA) (reactive arthritis, psoriatic arthritis (PsA) and undifferentiated SPA), rheumatoid arthritis (RA) and painful articular syndrome. Methods: We carried out a computer-assisted search of PubMed for the medical literature from January 1981 to January 2015 using the keywords HIV, acquired immune-deficiency syndrome, rheumatic manifestations, arthritis, spondyloarthropathy, anti-TNF and disease modifying antirheumatic drugs. Only English language literature was included and only studies involving adult human subjects were assessed. Results: There are challenges in the management of inflammatory arthritis in patients who are HIV-positive, including difficulties in the assessment of disease activity and limited information on the safety of immunosuppressive drugs in these individuals. Conclusions: This review focuses on the clinical characteristics of the inflammatory articular syndromes that have been described in association with HIV infection and discusses the therapeutic options for these patients

Effectiveness of Non-nucleoside Reverse-Transcriptase Inhibitor-Based Antiretroviral Therapy in Women Previously Exposed to a Single Intrapartum Dose of Nevirapine: A Multi-country, Prospective Cohort Study

In a comparative cohort study, Jeffrey Stringer and colleagues investigate the risk of ART failure in women who received single-dose nevirapine for PMTCT, and assess the duration of increased risk

Nitazoxanide for persistent diarrhoea in Zambian acquired immune deficiency syndrome patients: a randomized-controlled trial

Background: Adults with acquired immune deficiency syndrome and persistent diarrhoea in Zambia have intestinal infection, predominantly protozoa. Aim: To search for treatment which can be offered with minimal investigation, we carried out a double‐blind, randomized‐controlled trial of nitazoxanide (a drug with a range of activity against parasites and bacteria). Methods: Patients with diarrhoea of 1 month duration or longer were randomized to receive nitazoxanide (1000 mg twice daily) or placebo for 2 weeks. End‐points were clinical response, parasitological clearance and mortality. Results: Two hundred and seven adults were randomized; 42 died during the study. The primary assessment of efficacy was made after 17 days. Clinical response was observed in 56 (75%) of 75 patients receiving nitazoxanide and 45 (58%) of 77 patients receiving placebo (P = 0.03). The rate of improvement was markedly higher in patients with CD4 counts under 50 cells/μL receiving nitazoxanide (P = 0.007). The benefit was largely restricted to the period when the drug was being administered. No difference was seen in parasitological clearance between the two groups. Mortality was 19% by 4 weeks of follow‐up and did not differ with treatment allocation. Conclusions: Nitazoxanide given orally for 14 days was associated with clinical improvement in Zambian acquired immune deficiency syndrome patients with diarrhoea, especially those with very low CD4 counts

The effect of HIV infection on paediatric bacterial meningitis in Blantyre, Malawi

Aim: To compare presentation, progress, and outcome of acute bacterial meningitis in HIV seropositive and seronegative children. Methods: A double blind randomised placebo controlled study of the use of dexamethasone as adjuvant therapy in acute bacterial meningitis, in children aged 2 months to 13 years, was carried out from July 1997 to March 2001. A total of 598 children were enrolled, of whom 459 were tested for HIV serostatus. Results: Of the 459 children, 34% were HIV seropositive. Their presentation was similar to HIV seronegative children but more were shocked on arrival at hospital (33/157 v 12/302), and more had a focus of infection (85/157 v 57/302). HIV positive children had a higher incidence of Streptococcus pneumoniae infections (52% v 32%). Sixty four cases relapsed; 67% were in HIV positive patients. The mortality in HIV positive children was 65% compared with 36% in HIV negative children. The number of survivors in each group was similar. Hearing loss was more common in HIV negative than HIV positive children (66.3% v 47.2%). Steroid therapy had no influence on meningitis in HIV positive children, but the mortality in HIV negative children was 61% in children given steroids, and 39% in those who did not receive steroids. Conclusion: HIV seropositive children who develop bacterial meningitis have a high mortality and are prone to recurrent disease. There is an urgent need to prevent both primary and recurrent infections

Genetic analysis of circulating and sequestered populations of Plasmodium falciparum in fatal pediatric malaria

Falciparum malaria is characterized by cytoadherence of host erythrocytes containing mature asexual-stage parasites and the consequent sequestration of these forms in tissue microvasculature. A postmortem study of pediatric malaria provided us with the opportunity to compare the genetic complexity of circulating and sequestered Plasmodium falciparum populations, in patients with fatal cerebral malaria ( CM) versus control subjects with incidental P. falciparum parasitemia who died of causes other than malaria. Parasite genotypes identified in peripheral blood collected at the time of admission to the hospital constituted a subset of those detected in the tissues at death. Despite a higher tissue burden of parasitized erythrocytes in patients with CM than in parasitemic control subjects, parasite populations in tissues from patients with CM were less genetically complex, and the genotypes were more homogeneously distributed throughout the body, than in patients with incidental infection. Our findings support the notion that CM is associated with the emergence of a small number of dominant genotypes in an infected individual

An Assessment of the Risk Factors Associated with Disease Outbreaks across Tilapia Farms in Central and Southern Zambia

The study investigated the management practices that contribute to disease outbreaks in farmed tilapia in Lusaka and central and southern provinces in Zambia. It was a cross-sectional qualitative study undertaken from January to March 2021 in which questionnaires were administered to 49 farmers to assess their fish health management and biosecurity competence. Data were analysed using means, percentages, ratios, and logistical regression. The results showed that the majority of the farms had high stocking densities (>8 fish/m2, 44.4%), reared Nile tilapia (67.7%), and sourced water for farming from rivers and streams (45.7%). A few farmers measured water quality parameters daily (16.7%) and removed dead fish from ponds daily (20.8%). The stocking density (p = 0.013), fish species (p = 0.031), dead fish disposal methods (p = 0.023), and control of predator birds (p = 0.016) influenced the total mortality recorded on farms, while pond type (p = 0.031 and p = 0.045), water source (p = 0.023), and stocking density (p = 0.027) influenced the duration of a mortality episode. It is evident that some fish health management practices and biosecurity concepts among tilapia farmers in the study area are inadequate and may not contain disease outbreaks or the spread of pathogens