Pronounced interplay between intrinsic phase-coexistence and octahedral tilt magnitude in hole-doped lanthanum cuprates.

Definitive understanding of superconductivity and its interplay with structural symmetry in the hole-doped lanthanum cuprates remains elusive. The suppression of superconductivity around 1/8th doping maintains particular focus, often attributed to charge-density waves (CDWs) ordering in the low-temperature tetragonal (LTT) phase. Central to many investigations into this interplay is the thesis that La1.875Ba0.125CuO4 and particularly La1.675Eu0.2Sr0.125CuO4 present model systems of purely LTT structure at low temperature. However, combining single-crystal and high-resolution powder X-ray diffraction, we find these to exhibit significant, intrinsic coexistence of LTT and low-temperature orthorhombic domains, typically associated with superconductivity, even at 10 K. Our two-phase models reveal substantially greater tilting of CuO6 octahedra in the LTT phase, markedly buckling the CuO2 planes. This would couple significantly to band narrowing, potentially indicating a picture of electronically driven phase segregation, reminiscent of optimally doped manganites. These results call for reassessment of many experiments seeking to elucidate structural and electronic interplay at 1/8 doping.

An index of community ocular Chlamydia trachomatis load for control of trachoma.

Quantitative PCR (Q-PCR) technology has recently been applied to the measurement of ocular loads of Chlamydia trachomatis. We present an index called the community ocular C. trachomatis load (COCTL) which is similar to the community microfilarial load (CMFL) of onchocerciasis. Our index has the advantage of being scale-independent so that, for example, percentage changes are the same whether calculated per eye swab or per Q-PCR capillary. The COCTL for a population or subgroup is formed by adding the arbitrary concentration of 1 organism per ml to each individual Q-PCR quantification, calculating the geometric mean, and finally subtracting 1 per ml again. The use of the COCTL is illustrated in a study of trachoma in northern Tanzania. The COCTL is higher in people with clinical trachoma than those without (5.8 organisms per swab vs. 0.1), and in children aged six months to ten years than in the overall population (1.1 vs. 0.4). The COCTL index is potentially useful for sentinel sites, operational research and calibration of clinical measures of trachoma.

The household distribution of trachoma in a Tanzanian village: an application of GIS to the study of trachoma.

The distribution of active trachoma in Kahe Mpya, Tanzania, an endemic village of approximately 1000 people, was mapped spatially and analysed for associated risk factors and evidence of clustering. An association between distance to water source and active disease was demonstrated, although this was reduced after accounting for the lack of independence between cases in the same household. Significant clustering of active trachoma within households was demonstrated, adding support to the hypothesized importance of intra-familial transmission. The spatial distribution of trachoma was analysed using the spatial scan statistic, and evidence of clustering of active trachoma cases detected. Understanding the distribution of the disease has implications for understanding the dynamics of transmission and therefore appropriate control activities. The demonstrated spatial clustering suggests inter-familial as well as intra-familial transmission of infection may be common in this setting. The association between active trachoma and geographical information system (GIS) measured distance to water may be relevant for planning control measures.

Long term outcome of trichiasis surgery in the Gambia.

BACKGROUND: Trichiasis surgery is believed to reduce the risk of losing vision from trachoma. There are limited data on the long term outcome of surgery and its effect on vision and corneal opacification. Similarly, the determinants of failure are not well understood. METHODS: A cohort of people in the Gambia who had undergone surgery for trachomatous trichiasis 3-4 years earlier was re-assessed. They were examined clinically and the conjunctiva was sampled for Chlamydia trachomatis polymerase chain reaction (PCR) and general bacterial culture. RESULTS: In total, 141/162 people were re-examined. Recurrent trichiasis was found in 89/214 (41.6%) operated eyes and 52 (24.3%) eyes had five or more lashes touching the globe. Corneal opacification improved in 36 of 78 previously affected eyes. There was a general deterioration in visual acuity between surgery and follow up, which was greater if new corneal opacification developed or trichiasis returned. Recurrent trichiasis was associated with severe conjunctival inflammation and bacterial infection. C trachomatis was detected in only one individual. CONCLUSIONS: Recurrent trichiasis following surgery is a common potentially sight threatening problem. Some improvement in the cornea can occur following surgery and the rate of visual loss tended to be less in those without recurrent trichiasis. The role of conjunctival inflammation and bacterial infection needs to be investigated further. Follow up of patients is advised to identify individuals needing additional surgical treatment.

A randomised controlled trial of azithromycin following surgery for trachomatous trichiasis in the Gambia.

BACKGROUND/AIM: Trachomatous trichiasis frequently returns following surgery. Several factors may promote recurrence: preoperative disease severity, surgeon ability, surgical procedure, healing responses, and infection. This study investigates whether enhanced control of infection, both of Chlamydia trachomatis and other bacteria, with azithromycin can improve surgical outcome in a trachoma control programme. METHODS: Individuals with trachomatous trichiasis were examined and operated. After surgery patients were randomised to the azithromycin or control group. The azithromycin group and children in their household were given a dose of azithromycin. Antibiotic treatment was repeated at 6 months. All patients were reassessed at 6 months and 12 months. Samples were collected for C trachomatis polymerase chain reaction and general microbiology at each examination. RESULTS: 451 patients were enrolled. 426 (94%) were reassessed at 1 year, of whom 176 (41.3%) had one or more lashes touching the eye and 84 (19.7%) had five or more lashes. There was no difference in trichiasis recurrence between the azithromycin and control group. Recurrent trichiasis was significantly associated with more severe preoperative trichiasis, bacterial infection, and severe conjunctival inflammation at 12 months. Significant variability in outcome was found between surgeons. Visual acuity and symptoms significantly improved following surgery. CONCLUSION: In this setting, with a low prevalence of active trachoma, azithromycin did not improve the outcome of trichiasis surgery conducted by a trachoma control programme. Audit of trichiasis surgery should be routine.

Prevention of cerebral malaria in children in Papua New Guinea by southeast Asian ovalocytosis band 3.

Southeast Asian ovalocytosis (SAO) occurs at high frequency in malarious regions of the western Pacific and may afford a survival advantage against malaria. It is caused by a deletion of the erythrocyte membrane band 3 gene and the band 3 protein mediates the cytoadherence of parasitized erythrocytes in vitro. The SAO band 3 variant may prevent cerebral malaria but it exacerbates malaria anemia and may also increase acidosis, a major determinant of mortality in malaria. We undertook a case-control study of children admitted to hospital in a malarious region of Papua New Guinea. The SAO band 3, detected by the polymerase chain reaction, was present in 0 of 68 children with cerebral malaria compared with six (8.8%) of 68 matched community controls (odds ratio = 0, 95% confidence interval = 0-0.85). Median hemoglobin levels were 1.2 g/dl lower in malaria cases with SAO than in controls (P = 0.035) but acidosis was not affected. The remarkable protection that SAO band 3 affords against cerebral malaria may offer a valuable approach to a better understanding of the mechanisms of adherence of parasitized erythrocytes to vascular endothelium, and thus of the pathogenesis of cerebral malaria.

Acute disease episodes in a Wuchereria bancrofti-endemic area of Papua New Guinea.

Acute disease episodes of Bancroftian filariasis were monitored prospectively in a rural area of Papua New Guinea. The frequency and duration of episodes were recorded for the leg, arm, scrotum, and breast. A very high incidence of acute disease was observed; 0.31 episodes per person-year in the leg alone. Incidence generally increased with age, except in the breast, where episodes were concentrated in the reproductive age range. Males had slightly higher incidence than females in the leg and arm. Chronic disease was strongly associated with acute disease incidence in all locations. Microfilaremia had a statistically significant association with acute disease in the leg, arm, and breast, but not the scrotum. This study again demonstrates the high burden of acute manifestations of lymphatic filariasis, and provides new information on risk factors, which may lead to better understanding of etiology and control prospects.

Severe malaria in children in Papua New Guinea.

The clinical features of severe falciparum malaria and risk factors for mortality were studied in 489 children admitted with malaria to Madang Hospital, Papua New Guinea. The most common severe manifestations of malaria were severe anaemia (22%) and coma (16%). Children with severe anaemia were younger than those with coma (median age 2.2 vs. 3.7 years) and had been ill for longer before admission (median 7 vs. 4 days, respectively). Although the clinical features of coma in Madang children with malaria resembled closely those reported in African children, mortality was lower (8% vs. 17-25%, respectively). Overall, 17 (3.5%) children died, most within 12 h of admission. A high level of plasma lactate (> or = 5 mmol/l) was common (20%) and was the major predictor of death in multiple regression analysis. Raised plasma creatinine and decreased plasma bicarbonate were also independent predictors of mortality. Coma was not predictive of death, although a high proportion of children with profound coma died. Investigation of the causes of acidosis in children with malaria is a high research priority. In view of the short time interval between admission and death in many children, emphasis must be placed on the prevention or early recognition and treatment of acidosis in the district health clinic as well as the central hospital.

Occurrence of the erythrocyte band 3 (AE1) gene deletion in relation to malaria endemicity in Papua New Guinea.

South-east Asian ovalocytosis status was determined in 1629 individuals originating from 12 different geographical areas of Papua New Guinea, representing different ethnic groups and degrees of malaria endemicity. This was achieved by using polymerase chain reaction amplification to demonstrate a 27 base pair deletion in the erythrocyte band 3 (AE1) gene. By using this method, the prevalence of erythrocyte band 3 gene deletion was determined to range from zero in both the lowland inland area of Wosera, East Sepik Province and the highland region of Goroka, Eastern Highlands Province to 35% on the north coast of Madang Province. In general, the prevalence correlated well with altitude, being highest on the coast where malaria transmission is high, intermediate in the lowlands, and lowest in the non-malarious highlands. However, Wosera, a lowland area in the Sepik River Plains, which is hyperendemic for malaria, was an exception in that no ovalocytosis was detected. These results largely confirm the prevalence rates that have been reported in the past using microscopy. In keeping with the autosomal dominant mode of inheritance, the male:female ratio was 1.02 and no homozygote was detected, indicating that homozygosity for the ovalocytosis band 3 gene deletion is lethal.

Causes of preterm delivery and intrauterine growth retardation in a malaria endemic region of Papua New Guinea.

AIM: To identify causes of preterm delivery and intrauterine growth retardation (IUGR) in a malaria endemic region of Papua New Guinea. METHODS: Independent predictors of preterm delivery and birthweight in term infants were identified using multiple regression analysis in a prospective study of 987 singleton live births delivered in Madang Hospital. RESULTS: Overall, Plasmodium falciparum infection of the placenta was associated with a reduction in birthweight of 130 g. Malaria was significantly more common in primigravidae than multigravidae and probably contributed to both preterm delivery and IUGR. Maternal haemoglobin concentrations were significantly lower in malaria infected than noninfected women and reduced haemoglobin was the main determinant of preterm delivery. Poorer maternal nutritional status and smoking were associated with both prematurity and IUGR. Greater antenatal clinic attendance predicted increased birthweight in term infants. CONCLUSIONS: Protection against malaria during pregnancy, especially in primigravidae, improved nutrition in women and discouragement of smoking would probably reduce both preterm delivery and IUGR. Greater use of existing antenatal clinics might increase birthweight in term infants.

Design and analysis issues in cluster-randomized trials of interventions against infectious diseases.

This paper discusses the application of the cluster-randomized trial (CRT) design to evaluate the effectiveness of interventions against infectious diseases. In addition to the usual rationale for this design, there are a number of other advantages that are peculiar to the study of infectious diseases. In particular, CRTs are able to measure the overall effect of an intervention at the population level, capturing both the direct effect of an intervention on an individual's susceptibility to infection, and also the indirect effects due to changes in risks of transmission to other individuals, or to the mass effect or 'herd immunity' resulting from intervening in a large proportion of the population. We briefly review published CRTs of interventions against infectious diseases, most of which have been conducted in the developing countries where such diseases predominate. The focus is on trials in which communities or other large groupings are randomized, and in which impacts on infectious disease incidence or mortality are assessed. We then discuss three issues that are of special relevance to CRTs of infectious diseases. First, issues relating to the definition and size of clusters; secondly, the role of matching or stratification, and the choice of matching factors; and thirdly, the definition of direct and indirect effects of intervention, and methods of assessing these components in a CRT. We conclude by outlining some areas for future research.

Wuchereria bancrofti infection and disease in a rural area of Papua New Guinea.

The relation between infection and disease in lymphatic filariasis is still imperfectly understood. This paper presents baseline data on microfilaraemia, oedema and acute episodes from a drug trial against bancroftian filariasis in Papua New Guinea. Among 2,187 people with data on these manifestations, 1,144 were microfilaraemic, 78 had leg oedema, 356 had acute episodes and 919 were negative for all three. All possible combinations of the three manifestations were observed. The relationships between microfilaraemia and disease are found to be time-dependent. Microfilaraemia is a positive risk factor for leg oedema at lower ages, but a negative one at higher ages. Acute disease over a whole year is found to be positively associated with a point estimate of microfilaraemia. However, when considering incidence within a month of the time of the blood sample, a curvilinear relationship is found and people with low but positive microfilarial counts have the lowest incidence. Possible explanations for these findings are discussed.

Towards eliminating lymphatic filariasis in Papua New Guinea: impact of annual single-dose mass treatment on transmission of Wuchereria bancrofti in East Sepik Province.

The impact of annual single-dose community-wide treatment on the transmission of Wuchereria bancrofti was investigated in 5 villages in the East Sepik Province where pretreatment prevalence of microfilaraemia ranged from 34% to 73%. Anopheles punctulatus and An. koliensis were the only carriers of the parasite. 3 villages received diethylcarbamazine citrate (DEC) in combination with ivermectin (IVR) and 2 received DEC alone. The rate and intensity of microfilaraemia were both reduced in all 5 villages. Reduction in prevalence was between 43% and 67% in the DEC+IVR study villages and between 24% and 27% in the DEC alone villages. Density was reduced by between 81% and 95% in the DEC+IVR villages and between 69% and 74% in the DEC alone villages. Breaks in perennial transmission (failure to detect infective mosquitoes in four or more consecutive monthly collections) occurred in all 3 communities treated with DEC+IVR. Transmission was almost completely interrupted in 2 villages, where infective mosquitoes were not detected during 11 of the 12 months following treatment. We concluded that repeated annual single-dose community-wide treatment with DEC+IVR could lead to complete interruption of transmission and ultimately elimination of lymphatic filariasis.

Distance to water source and altitude in relation to active trachoma in Rombo district, Tanzania.

OBJECTIVES: To investigate the relationship between distance to water source, altitude and active trachoma in children in Rombo district, Tanzania. METHODS: In each of Rombo's 64 villages, 10 balozis (groups of 8-40 households) were selected at random and all resident children aged 1-9 years were examined for clinical signs of active trachoma. The households of these children and village water sources were mapped using differentially corrected global positioning system data to determine each household's altitude and distance to the nearest water supply. RESULTS: We examined 12 415 children and diagnosed 1171 cases of active trachoma (weighted prevalence=9.1%, 95% CI: 8.0, 10.2%). Active trachoma prevalence ranged from 0% to 33.7% across villages. Increasing distance to the nearest water source was significantly associated with rising trachoma prevalence (age-adjusted odds ratio for infection (OR) for highest quartile compared to lowest=3.56, 95% CI 2.47, 5.14, P for trend <0.0001). Altitude was significantly inversely associated with trachoma prevalence (age-adjusted OR for highest quartile compared to lowest=0.55, 95% CI 0.41, 0.75, P for trend <0.0001). These associations remained significant after adjustment in multivariate analysis. CONCLUSIONS: Trachoma is endemic in Rombo district, although the prevalence varies considerably between villages. Spatial mapping is a useful method for analysing risk factors for active trachoma.

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci.

Experimental evidence implicates interferon gamma (IFNgamma) in protection from and resolution of chlamydial infection. Conversely, interleukin 10 (IL10) is associated with susceptibility and persistence of infection and pathology. We studied genetic variation within the IL10 and IFNgamma loci in relation to the risk of developing severe complications of human ocular Chlamydia trachomatis infection. A total of 651 Gambian subjects with scarring trachoma, of whom 307 also had potentially blinding trichiasis and pair-matched controls with normal eyelids, were screened for associations between single-nucleotide polymorphisms (SNPs), SNP haplotypes and the risk of disease. MassEXTEND (Sequenom) and MALDI-TOF mass spectrometry were used for detection and analysis of SNPs and the programs PHASE and SNPHAP used to infer haplotypes from population genetic data. Multivariate conditional logistic regression analysis identified IL10 and IFNgamma SNP haplotypes associated with increased risk of both trachomatous scarring and trichiasis. SNPs in putative IFNgamma and IL10 regulatory regions lay within the disease-associated haplotypes. The IFNgamma +874A allele, previously linked to lower IFNgamma production, lies in the IFNgamma risk haplotype and was more common among cases than controls, but not significantly so. The promoter IL10-1082G allele, previously associated with high IL10 expression, is in both susceptibility and resistance haplotypes.