Project EURISGIC : worst case scenarios (technical note D5.1)

The overall objective of Work Package 5 of the EURISGIC project (see website eurisgic.eu) is defined as being: “Estimate the largest possible GIC flowing anywhere in the European high-voltage power grid, based on archive data.” This document is a technical note (deliverable item D5.1) for the results of this work package. For each of the project team members participating in the work package (FMI – Finland; Neurospace – Sweden; IRF – Sweden; NASA and Catholic University of America - USA; BGS - UK) we summarise activities related to worst case scenario modelling: activities such as research into extreme event statistical methods, theoretical extreme event modelling and individual (historical and hypothetical) event studies. We note that research is continuing and therefore some results reported here are subject to further confirmation in published scientific journals

Trends and measurement of HIV prevalence in northern Malawi.

BACKGROUND: Most data on HIV prevalence in Malawi come from antenatal clinic (ANC) surveillance and are, therefore, subject to bias. OBJECTIVES: HIV prevalence and risk factors were measured using population-based data to assess the accuracy of ANC surveillance and changes in prevalence and risk factors for HIV over time. METHODS: HIV prevalence was measured in 1988-1993 and 1998-2001 in community controls from case-control studies of mycobacterial disease in Karonga District, Malawi. ANC surveillance studies in the district began in 1999. RESULTS: Age and area-standardized HIV prevalence in women aged 15-49 years in the community was 3.9% in 1988-1990, 12.5% in 1991-1993 and 13.9% in 1998-2001. For men, HIV prevalence was 3.7%, 9.2% and 11.4% in the same periods. In 1988-1993, HIV positivity was associated with occupations other than farming, with increased schooling and being born outside Karonga District. In 1998-2001, non-farmers were still at higher risk but the other associations were not seen. The age- and area-adjusted HIV prevalence in the ANC in 1999-2001 was 9.2%. The underestimate can be explained largely by marriage and mobility. Reduced fertility in HIV-positive individuals was demonstrated in both ANC and community populations. A previously recommended parity-based adjustment gave an estimated female HIV prevalence of 15.0%. CONCLUSIONS: HIV prevalence has increased and continues to be higher in non-farmers. The increase is particularly marked in those with no education. ANC surveillance underestimated HIV prevalence in the female population in all but the youngest age group. Although there were differences in sociodemographic factors, a parity-based adjustment gave a reasonable estimate of female HIV prevalence

The importance of recent infection with Mycobacterium tuberculosis in an area with high HIV prevalence: a long-term molecular epidemiological study in Northern Malawi.

BACKGROUND: The proportion of cases of tuberculosis due to recent infection can be estimated in long-term population-based studies using molecular techniques. Here, we present what is, to our knowledge, the first such study in an area with high human immunodeficiency virus (HIV) prevalence. METHODS: All patients with tuberculosis in Karonga District, Malawi, were interviewed. Isolates were genotyped using restriction-fragment-length polymorphism (RFLP) patterns. Strains were considered to be "clustered" if at least 1 other patient had an isolate with an identical pattern. RESULTS: RFLP results were available from 83% of culture-positive patients from late 1995 to early 2003. When strains with <5 bands were excluded, 72% (682/948) were clustered. Maximum clustering was reached using a 4-year window, with an estimated two-thirds of cases due to recent transmission. The proportion clustered decreased with age and varied by area of residence. In older adults, clustering was less common in men and more common in patients who were HIV positive (adjusted odds ratio, 5.1 [95% confidence interval, 2.1-12.6]). CONCLUSIONS: The proportion clustered found in the present study was among the highest in the world, suggesting high rates of recent transmission. The association with HIV infection in older adults may suggest that HIV has a greater impact on disease caused by recent transmission than on that caused by reactivation

Persisting high prevalence of pneumococcal carriage among HIV-infected adults receiving antiretroviral therapy in Malawi:a cohort study

OBJECTIVE: HIV-infected adults have high rates of pneumococcal carriage and invasive disease. We investigated the effect of antiretroviral therapy (ART) on pneumococcal carriage in HIV-infected adults prior to infant pneumococcal conjugate vaccine (PCV) rollout. DESIGN: Observational cohort study. METHODS: We recruited HIV-infected adults newly attending a rural HIV clinic in northern Malawi between 2008 and 2010. Nasopharyngeal samples were taken at baseline and after 6, 12, 18 and 24 months. We compared pneumococcal carriage by ART status using generalized estimated equation models adjusted for CD4 cell count, sex, seasonality, and other potential confounders. RESULTS: In total, 336 individuals were included, of which 223 individuals started ART during follow-up. Individuals receiving ART had higher pneumococcal carriage than individuals not receiving ART (25.9 vs. 19.8%, P = 0.03) particularly for serotypes not included in PCV13 (16.1 vs. 9.6% P = 0.003). Following adjustment, increased carriage of non-PCV13 serotypes was still observed for individuals on ART, but results for all serotypes were nonsignificant [all serotypes: adjusted risk ratio (aRR) 1.22 (0.95-1.56); non-PCV13 serotypes: aRR 1.72, 95% CI 1.13-2.62]. CONCLUSION: Pneumococcal carriage in HIV-infected adults in Malawi remained high despite use of ART, consistent with failure of mucosal immune reconstitution in the upper respiratory tract. There was evidence of increased carriage of non-PCV13 serotypes. HIV-infected adults on ART could remain an important reservoir for pneumococcal diversity post infant pneumococcal vaccine introduction. Control of pneumococcal disease in African HIV remains a priority

Effect of human rotavirus vaccine on severe diarrhea in African infants.

BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. METHODS: We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale. RESULTS: A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. CONCLUSIONS: Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.

Reverse transcriptase drug resistance mutations in HIV-1 subtype C infected patients on ART in Karonga District, Malawi

<p>Abstract</p> <p>Background</p> <p>Drug resistance testing before initiation of, or during, antiretroviral therapy (ART) is not routinely performed in resource-limited settings. High levels of viral resistance circulating within the population will have impact on treatment programs by increasing the chances of transmission of resistant strains and treatment failure. Here, we investigate Drug Resistance Mutations (DRMs) from blood samples obtained at regular intervals from patients on ART (Baseline-22 months) in Karonga District, Malawi. One hundred and forty nine reverse transcriptase (RT) consensus sequences were obtained via nested PCR and automated sequencing from blood samples collected at three-month intervals from 75 HIV-1 subtype C infected individuals in the ART programme.</p> <p>Results</p> <p>Fifteen individuals showed DRMs, and in ten individuals DRMs were seen from baseline samples (reported to be ART naïve). Three individuals in whom no DRMs were observed at baseline showed the emergence of DRMs during ART exposure. Four individuals who did show DRMs at baseline showed additional DRMs at subsequent time points, while two individuals showed evidence of DRMs at baseline and either no DRMs, or different DRMs, at later timepoints. Three individuals had immune failure but none appeared to be failing clinically.</p> <p>Conclusion</p> <p>Despite the presence of DRMs to drugs included in the current regimen in some individuals, and immune failure in three, no signs of clinical failure were seen during this study. This cohort will continue to be monitored as part of the Karonga Prevention Study so that the long-term impact of these mutations can be assessed. Documenting proviral population is also important in monitoring the emergence of drug resistance as selective pressure provided by ART compromises the current plasma population, archived viruses can re-emerge</p

Pneumococcal acquisition among infants exposed to HIV in rural Malawi:a longitudinal household study

The prevalence of Streptococcus pneumoniae (pneumococcus) carriage is higher in adults who are infected with human immunodeficiency virus (HIV) than in adults who are not. We hypothesized that infants exposed to HIV become carriers of nasopharyngeal pneumococcus earlier and more frequently than infants who are not exposed to HIV. We compared infant pneumococcal acquisition by maternal HIV status and household exposure in Karonga District, Malawi, in 2009-2011, before the introduction of pneumococcal conjugate vaccine. Nasopharyngeal swabs were collected every 4-6 weeks in the first year of life from infants with known HIV-exposure status, their mothers, and other household members. We studied infant pneumococcal acquisition by maternal HIV status, serotype-specific household exposure, and other risk factors, including seasonality. We recruited 54 infants who were exposed to HIV and 131 infants who were not. There was no significant difference in pneumococcal acquisition by maternal HIV status (adjusted rate ratio (aRR) = 1.00, 95% confidence interval (CI): 0.87, 1.15). Carriage by the mother was associated with greater acquisition of the same serotype (aRR = 3.09, 95% CI: 1.47, 6.50), but the adjusted population attributable fraction was negligible (1.9%, 95% CI: 0.0, 4.3). Serotype-specific exposure to children under 5 years of age was associated with higher acquisition (aRR = 4.30, 95% CI: 2.80, 6.60; adjusted population attributable fraction = 8.8%, 95% CI: 4.0, 13.4). We found no evidence to suggest that maternal HIV infection would affect the impact of pneumococcal vaccination on colonization in this population

Effect of human rotavirus vaccine on severe diarrhea in African infants

BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. METHODS: We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine — the pooled vaccine group — or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale. RESULTS: A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. CONCLUSIONS: Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.

Improving the productivity and resilience of smallholder farmers with maize-legume and legume-legume systems in Malawi

Smallholder farmers in southern africa must cope with declining soil fertility and production risks associated with frequent droughts (jayne et al., 2014). Legume integration through rotations or intercropping in maize-based farming systems are promoted to increase crop diversification and soil fertility. Anovel strategy, doubled up legumes, could help develop production systems that fulfil sustainable intensification (SI) indicators. It is however crucial to understand resource competition in mixed cropping systems under variable soil and climate conditions

The impact of long-term azithromycin on antibiotic resistance in HIV-associated chronic lung disease

Selection for resistance to azithromycin (AZM) and other antibiotics such as tetracyclines and lincosamides remains a concern with long-term AZM use for treatment of chronic lung diseases (CLD). We investigated the impact of 48 weeks of AZM on the carriage and antibiotic resistance of common respiratory bacteria among children with HIV-associated CLD. Nasopharyngeal (NP) swabs and sputa were collected at baseline, 48 and 72 weeks from participants with HIV-associated CLD randomised to receive weekly AZM or placebo for 48 weeks and followed postintervention until 72 weeks. The primary outcomes were prevalence and antibiotic resistance of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI) and Moraxella catarrhalis (MC) at these timepoints. Mixed-effects logistic regression and Fisher’s exact test were used to compare carriage and resistance, respectively. Of 347 (174 AZM, 173 placebo) participants (median age 15 years (IQR 13–18), female 49%), NP carriage was significantly lower in the AZM (n=159) compared to placebo (n=153) arm for SP (18% versus 41%, p<0.001), HI (7% versus 16%, p=0.01) and MC (4% versus 11%, p=0.02); SP resistance to AZM (62% (18 out of 29) versus 13% (8 out of 63), p<0.0001) or tetracycline (60% (18 out of 29) versus 21% (13 out of 63), p<0.0001) was higher in the AZM arm. Carriage of SA resistant to AZM (91% (31 out of 34) versus 3% (1 out of 31), p<0.0001), tetracycline (35% (12 out of 34) versus 13% (4 out of 31), p=0.05) and clindamycin (79% (27 out of 34) versus 3% (1 out of 31), p<0.0001) was also significantly higher in the AZM arm and persisted at 72 weeks. Similar findings were observed for sputa. The persistence of antibiotic resistance and its clinical relevance for future infectious episodes requiring treatment needs further investigation