Kim A. Lindblade

A distinct lineage of influenza A virus from bats

Influenza A virus reservoirs in animals have provided novel genetic elements leading to the emergence of global pandemics in humans. Most influenza A viruses circulate in waterfowl, but those that infect mammalian hosts are thought to pose the greatest risk for zoonotic spread to humans and the generation of pandemic or panzootic viruses. We have identified an influenza A virus from little yellow-shouldered bats captured at two locations in Guatemala. It is significantly divergent from known influenza A viruses. The HA of the bat virus was estimated to have diverged at roughly the same time as the known subtypes of HA and was designated as H17. The neuraminidase (NA) gene is highly divergent from all known influenza NAs, and the internal genes from the bat virus diverged from those of known influenza A viruses before the estimated divergence of the known influenza A internal gene lineages. Attempts to propagate this virus in cell cultures and chicken embryos were unsuccessful, suggesting distinct requirements compared with known influenza viruses. Despite its divergence from known influenza A viruses, the bat virus is compatible for genetic exchange with human influenza viruses in human cells, suggesting the potential capability for reassortment and contributions to new pandemic or panzootic influenza A viruses.

Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis

BACKGROUND The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years. METHODS We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. FINDINGS We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. INTERPRETATION Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. FUNDING WHO; Bill & Melinda Gates Foundation.

Use of antenatal services and delivery care among women in rural western Kenya: a community based survey

BackgroundImproving maternal health is one of the UN Millennium Development Goals. We assessed provision and use of antenatal services and delivery care among women in rural Kenya to determine whether women were receiving appropriate care.MethodsPopulation-based cross-sectional survey among women who had recently delivered.ResultsOf 635 participants, 90% visited the antenatal clinic (ANC) at least once during their last pregnancy (median number of visits 4). Most women (64%) first visited the ANC in the third trimester; a perceived lack of quality in the ANC was associated with a late first ANC visit (Odds ratio [OR] 1.5, 95% confidence interval [CI] 1.0–2.4). Women who did not visit an ANC were more likely to have < 8 years of education (adjusted OR [AOR] 3.0, 95% CI 1.5–6.0), and a low socio-economic status (SES) (AOR 2.8, 95% CI 1.5–5.3). The ANC provision of abdominal palpation, tetanus vaccination and weight measurement were high (>90%), but provision of other services was low, e.g. malaria prevention (21%), iron (53%) and folate (44%) supplementation, syphilis testing (19.4%) and health talks (14.4%). Eighty percent of women delivered outside a health facility; among these, traditional birth attendants assisted 42%, laypersons assisted 36%, while 22% received no assistance. Factors significantly associated with giving birth outside a health facility included: age ≥ 30 years, parity ≥ 5, low SES, < 8 years of education, and > 1 hour walking distance from the health facility. Women who delivered unassisted were more likely to be of parity ≥ 5 (AOR 5.7, 95% CI 2.8–11.6).ConclusionIn this rural area, usage of the ANC was high, but this opportunity to deliver important health services was not fully utilized. Use of professional delivery services was low, and almost 1 out of 5 women delivered unassisted. There is an urgent need to improve this dangerous situation.

Land use change alters malaria transmission parameters by modifying temperature in a highland area of Uganda

Summary As highland regions of Africa historically have been considered free of malaria, recent epidemics in these areas have raised concerns that high elevation malaria transmission may be increasing. Hypotheses about the reasons for this include changes in climate, land use and demographic patterns. We investigated the effect of land use change on malaria transmission in the south‐western highlands of Uganda. From December 1997 to July 1998, we compared mosquito density, biting rates, sporozoite rates and entomological inoculation rates between 8 villages located along natural papyrus swamps and 8 villages located along swamps that have been drained and cultivated. Since vegetation changes affect evapotranspiration patterns and, thus, local climate, we also investigated differences in temperature, humidity and saturation deficit between natural and cultivated swamps. We found that on average all malaria indices were higher near cultivated swamps, although differences between cultivated and natural swamps were not statistically significant. However, maximum and minimum temperature were significantly higher in communities bordering cultivated swamps. In multivariate analysis using a generalized estimating equation approach to Poisson regression, the average minimum temperature of a village was significantly associated with the number of Anopheles gambiae s.l. per house after adjustment for potential confounding variables. It appears that replacement of natural swamp vegetation with agricultural crops has led to increased temperatures, which may be responsible for elevated malaria transmission risk in cultivated areas.

Highland malaria in Uganda: Prospective analysis of an epidemic associated with El Niño

Malaria epidemics in African highlands cause serious morbidity and mortality and are being reported more frequently. Weather is likely to play an important role in initiating epidemics but limited analysis of the association between weather conditions and epidemic transmission parameters has been undertaken. We measured entomological variables before and during an epidemic of malaria (which began in February 1998) in a highland region of south-western Uganda and analysed temporal variation in weather data against malaria incidence (estimated from clinic records), mosquito density and entomological inoculation rates (EIR). Indoor resting density of Anopheles gambiae s.l. was positively correlated with malaria incidence (r = 0.68, P < 0.05) despite extremely low vector densities. EIR totalled only 0.41 infectious bites per person during the entire 8-month study period. Rainfall during and following the El Niño event in 1997 was much higher than normal, and rainfall anomaly (difference from the mean) was positively correlated with vector density 1 month later (r = 0.55, P < 0.05). Heavier than normal rainfall associated with El Niño may have initiated the epidemic; the relationship between temperature and transmission parameters remains to be defined. The results from this study indicate that, in this highland population, epidemic malaria may occur at extremely low inoculation rates.

Bats are a major natural reservoir for hepaciviruses and pegiviruses

Although there are over 1,150 bat species worldwide, the diversity of viruses harbored by bats has only recently come into focus as a result of expanded wildlife surveillance. Such surveys are of importance in determining the potential for novel viruses to emerge in humans, and for optimal management of bats and their habitats. To enhance our knowledge of the viral diversity present in bats, we initially surveyed 415 sera from African and Central American bats. Unbiased high-throughput sequencing revealed the presence of a highly diverse group of bat-derived viruses related to hepaciviruses and pegiviruses within the family Flaviridae. Subsequent PCR screening of 1,258 bat specimens collected worldwide indicated the presence of these viruses also in North America and Asia. A total of 83 bat-derived viruses were identified, representing an infection rate of nearly 5%. Evolutionary analyses revealed that all known hepaciviruses and pegiviruses, including those previously documented in humans and other primates, fall within the phylogenetic diversity of the bat-derived viruses described here. The prevalence, unprecedented viral biodiversity, phylogenetic divergence, and worldwide distribution of the bat-derived viruses suggest that bats are a major and ancient natural reservoir for both hepaciviruses and pegiviruses and provide insights into the evolutionary history of hepatitis C virus and the human GB viruses.

The silent threat: asymptomatic parasitemia and malaria transmission

Scale-up of malaria control interventions has resulted in a substantial decline in global malaria morbidity and mortality. Despite this achievement, there is evidence that current interventions alone will not lead to malaria elimination in most malaria-endemic areas and additional strategies need to be considered. Use of antimalarial drugs to target the reservoir of malaria infection is an option to reduce the transmission of malaria between humans and mosquito vectors. However, a large proportion of human malaria infections are asymptomatic, requiring treatment that is not triggered by care-seeking for clinical illness. This article reviews the evidence that asymptomatic malaria infection plays an important role in malaria transmission and that interventions to target this parasite reservoir may be needed to achieve malaria elimination in both low- and high-transmission areas.

Health and nutritional status of orphans <6 years old cared for by relatives in western Kenya.

One of the consequences of the HIV/AIDS epidemic in sub‐Saharan Africa is the increase in the number of orphans, estimated to have reached 6–11% of children <15 years old in 2000. Orphans who stay in their communities may be at increased risk for poor health due to reduced circumstances and loss of parental care. We have used data from a population‐based study in rural western Kenya to compare basic health and nutritional indicators between non‐orphaned children <6 years old and children who lost either or both of their parents. In June 2000, all children <6 years old who had been recruited for a cross‐sectional survey in 60 villages of Rarieda Division, western Kenya, in June 1999 were invited to return for a follow‐up survey. Basic demographic characteristics, including the vital status of the childs parents, and health histories were requested from all 1190 participants of the follow‐up survey, along with a finger‐prick blood sample for determination of malaria parasite status and haemoglobin (Hb) levels. Height‐for‐age (H/A) and weight‐for‐height (W/H) Z‐scores were also calculated from anthropometric measurements. Overall, 7.9% of the children had lost one or both their parents (6.4% had lost their father, 0.8% had lost their mother and 0.7% had lost both parents). While there was no difference between orphans and non‐orphans regarding most of the key health indicators (prevalence of fever and malaria parasitaemia, history of illness, Hb levels, H/A Z scores), W/H Z‐scores in orphans were almost 0.3 standard deviations lower than those of non‐orphans. This association was more pronounced among paternal orphans and those who had lost a parent more than 1 year ago. These results suggest that the health status of surviving orphans living in their community is similar to that of the non‐orphan population, but longitudinal cohort studies should be conducted to determine better the overall impact of orphanhood on child health.

Evaluation of long-lasting insecticidal nets after 2 years of household use.

Development of long‐lasting insecticidal nets (LLINs) may eliminate the need for insecticide retreatment of ITNs. While two LLINs (Olyset®, Sumitomo Chemical Co., Japan; and PermaNet® 1.0, Vestergaard‐Frandsen, Denmark) have received recommendations from the World Health Organization Pesticide Evaluation Scheme, field‐testing under normal use has been limited. We used a survival analysis approach to compare time to net failure of conventional polyester bednets treated only with deltamethrin to two LLINs and two candidate LLINs (Olyset®; PermaNet®; Insector, Athanor, France; and Dawa®, Siamdutch Mosquito Netting Co., Thailand). Additionally, we evaluated nets treated with a process designed to increase the wash‐durability of permethrin‐treated nets through the addition of cyclodextrin (a starch) in the treatment process. Houses in western Kenya were randomly assigned to one of the six net types and nets were distributed to cover all sleeping spaces. Households were visited monthly to assess reported side effects in inhabitants and washing frequency. Nets were evaluated for insecticidal activity by periodic WHO cone bioassays with mortality assessed at 24 h. Nets with bioassay mortality <70% were assayed monthly until failure, defined as the first of two consecutive bioassay mortality rates <50%. Time to failure was analyzed using an extended Cox Proportional Hazards model controlling for the cumulative number of washes. We distributed 314 nets to 177 households in June–July 2002; 22 nets (7.0%) were lost to follow‐up and 196 (62.4%) failed during the first 2 years of the evaluation. Controlling for cumulative number of washes, PermaNet® 1.0 [Hazard Ratio (HR) 0.14, 95% Confidence Interval (CI) 0.06–0.31] had a significantly lower risk of failure than conventional nets while Insector had a significantly higher risk of failure (HR 2.57, 95% CI 1.06–4.15). The risks of failure of the remaining nets (Olyset®: HR 1.29, 95% CI 0.79–2.10; Dawa®: HR 0.58, 95% CI 0.32–1.18; cyclodextrin: HR 0.65, 95% CI 0.40–1.1) were not significantly different from that of a conventional net. PermaNet® 1.0 performed significantly better than conventional nets and should be recommended to malaria control programs.

Laboratory wash resistance of long-lasting insecticidal nets

Long‐lasting insecticidal nets (LLINs) may eliminate the need for retreatment of mosquito nets used for the control of malaria and other vector‐borne diseases. The efficacy of LLINs after repeated washing under laboratory conditions has been used to predict long‐lasting efficacy under field conditions. We evaluated under laboratory conditions the wash resistance of two LLINs (PermaNet® 1.0, Vestergaard‐Frandsen, Denmark; Olyset®, Sumitomo Chemical Co., Japan), two candidate LLINs (Dawa®, Siamdutch Mosquito Netting Co., Thailand; Insector, Athanor, France) and a net treated with a process designed to increase its wash resistance and compared them with conventionally treated nets (deltamethrin, 25 mg/m2). Nets of all six types were washed using a standard protocol and tested weekly using WHO cone bioassays with Anopheles gambiae (Kisumu strain). The PermaNet® 1.0 was the most wash resistant with >50% mosquito mortality in WHO cone bioassays after as many as 20 washes. The Dawa® net also retained some activity after repeated washing but exhibited wide variation in insecticide retention and biological activity. The remaining nets lost >90% of their biological activity after six washes as measured by 24‐h mortality of A. gambiae in WHO cone tests. After 20 washes, all nets lost >50% of their initial insecticide concentrations except for the Olyset® net. After 20 washes, nets were heated for 4 h at 60 °C to determine whether biological activity could be restored by heat‐assisted regeneration. Only the Olyset® net was regenerated by heating, with average mosquito mortality and knockdown in WHO cone tests rising to >90% after heating for 4 h at 60 °C. However, regeneration of the biological activity of Olyset® nets that had been washed three times did not occur at 30 °C or 35 °C after 12 weeks. The wash resistance of these LLINs corresponded well to their retention of biological activity observed in a field trial, suggesting that wash resistance may be a good predictor of the longevity of insecticidal activity of LLINs under field conditions.