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

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

Cytokine activation is predictive of mortality in Zambian patients with AIDS-related diarrhoea

Abstract Background Mortality in Zambian AIDS patients is high, especially in patients with diarrhoea, and there is still unacceptably high mortality in Zambian patients just starting anti-retroviral therapy. We set out to determine if high concentrations of serum cytokines correlate with mortality. Methods Serum samples from 30 healthy controls (HIV seropositive and seronegative) and 50 patients with diarrhoea (20 of whom died within 6 weeks) were analysed. Concentrations of tumour necrosis factor receptor p55 (TNFR p55), macrophage migration inhibitory factor (MIF), interleukin (IL)-6, IL-12, interferon (IFN)-γ and C-reactive protein (CRP) were measured by ELISA, and correlated with mortality after 6 weeks follow-up. Results Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends. In a multivariable analysis high TNFR p55, IFN-γ, CRP and low CD4 count (CD4 count Conclusion High serum concentrations of TNFR p55, IFN-γ, CRP and low CD4 count correlated with disease severity and short-term mortality in HIV-infected Zambian adults with diarrhoea. These factors were better predictors of survival than BMI. Understanding the cause of TNFR p55, IFN-γ and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa.</p

Findings from a comprehensive diarrhoea prevention and treatment programme in Lusaka, Zambia

Abstract Background The Programme for the Awareness and Elimination of Diarrhoea (PAED) was a pilot comprehensive diarrhoea prevention and control programme aimed to reduce post-neonatal, all-cause under-five mortality by 15 % in Lusaka Province. Interventions included introduction of the rotavirus vaccine, improved clinical case management of diarrhoea, and a comprehensive community prevention and advocacy campaign on hand washing with soap, exclusive breastfeeding up to 6 months of age, and the use of ORS and Zinc. This study aimed to assess the impact of PAED on under-5 mortality. Methods The study was a pre-post evaluation design. The Demographic and Health Survey style population-based two-stage approach was used to collect data at the beginning of the intervention and 3 years following the start of intervention implementation in Lusaka province. The primary outcome of interest was an all-cause, post-neonatal under-five mortality rate defined as the probability of dying after the 28th day and before the fifth birthday among children aged 1–59 months. The Kaplan-Meier time to event analysis was used to estimate the probability of death; multiplying this probability by 1000 to yield the post-neonatal mortality rate. Survival-time inverse probability weighting model was used to estimate Average Treatment Effect (ATE). Results The percentage of children under age 5 who had diarrhoea in the last 2 weeks preceding the survey declined from 15.8 % (95 % CI: 15.2 %, 16.4 %) in 2012 to 12.7 % (95 % CI: 12.3 %, 13.2 %) in 2015. Over the same period, mortality in post-neonatal children under 5 years of age declined by 34 %, from an estimated rate of 29 deaths per 1000 live births (95 % CI: (26, 32) death per 1000 live births) to 19 deaths per 1000 live births (95 % CI: (16, 21) death per 1000 live births). When every child in the population of children aged 1–59 months is exposed to the intervention, the average time-to-death was estimated to be about 8 months more than when no child is exposed (ATE = 7.9; 95 % CI: 4.4,11.5; P < 0.001). Conclusion Well-packaged diarrhoea preventive and treatment interventions delivered at the clinic and community-level could potentially reduce probability of death among children aged 1–59 months

Time between exposure to single-dose NVP and starting antiretroviral therapy and the probability of treatment failure in the NNRTI Response Study—Zambia, Kenya, Thailand (2005–2008).

<p>Locally weighted regression (LOESS) models of the risk of treatment failure as a function of the time interval between NVP ingestion and starting ART. The left panel defines treatment failure according to the study's primary definition; the right panel defines treatment failure according to a planned secondary definition (see <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000233#s3" target="_blank">Methods</a>). The horizontal dotted line indicates the failure rate among the women who were not exposed to single-dose NVP. The individual plusses (+) indicated on each panel represent individual patients who were either failing (top) or not failing (bottom).</p

Baseline characteristics of participants enrolled in the NNRTI Response Study—Zambia, Kenya, Thailand (2005–2008).

<p>*<i>p</i>-Value<0.05, compared to Zambia by Wilcoxon rank-sum test.</p

Baseline characteristics of participants enrolled by prior exposure to single-dose nevirapine in the NNRTI Response Study—Zambia, Kenya, Thailand (2005–2008).

<p>*<i>p</i>-Value<0.05, compared to unexposed by Wilcoxon rank-sum test.</p

Factors associated with treatment failure in the primary analysis in the NNRTI Response Study—Zambia, Kenya, Thailand (2005–2008).

<p>See <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000233#s3" target="_blank">Methods</a> for definition of primary analysis.</p>a<p>Adjusted ORs controlling for country, CD4 cell count, viral load, WHO stage, age, hemoglobin, and body mass index (all as categorical variables as in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000233#pmed-1000233-t001" target="_blank">Table 1</a>. Twenty-one observations are not included, owing to missing baseline results for either viral load or hemoglobin.</p><p>Ref, referent group.</p

Studies of virologic response rates to NNRTI-based treatment among women previously exposed to single-dose NVP.

a<p>Some studies report outcomes at additional time points that are not listed here.</p>b<p>Women who received ZDV or ZDV/3TC typically received the regimen from ∼36 wk gestation.</p>c<p>Numbers of patients includes those from whom a virologic response was available in the report.</p>d<p>Proportions estimated by Kaplan-Meier method for references <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000233#pmed.1000233-Lockman1" target="_blank">[17]</a> and <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000233#pmed.1000233-Coovadia1" target="_blank">[28]</a>. All others are raw proportions.</p>e<p>Women who received NVP for PMTCT in this study got SDNVP alone, ZDV + SDNVP, or ZDV/3TC + SDNVP. Response rates listed here are from <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000233#pmed-1000233-t003" target="_blank">Table 3</a> in reference <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000233#pmed.1000233-Kuhn1" target="_blank">[27]</a>. <i>p</i>-Value calculated using Fisher's exact test.</p>f<p>All women in Thailand who were exposed to SDNVP also received antenatal ZDV; in Zambia and Kenya antenatal ZDV was not used. <i>p</i>-Values calculated using Fisher's exact test for each exposure interval compared to SDNVP unexposed.</p><p>SDNVP, single dose intrapartum nevirapine.</p

Interval between exposure to single-dose nevirapine and starting NNRTI-based antiretroviral therapy in the NNRTI Response Study—Zambia, Kenya, Thailand (2005 – 2008).

<p>Interval between exposure to single-dose nevirapine and starting NNRTI-based antiretroviral therapy in the NNRTI Response Study—Zambia, Kenya, Thailand (2005 – 2008).</p