Bulletin of the World Health Organisation

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Article
During the last quarter-century or so there has been a revolution in both health and information technology. For the globe as a whole we have seen tremendous strides made in life expectancy and disease control, together with an explosion of information technology and techniques. Humanity now has the potential to make all existing health knowledge available simultaneously to the entire population of the planet. By no means everyone has benefited from the overall trend of increased life expectancy, however, or from that of increased knowledge and its communicability. This gap goes beyond the notion of the "digital divide". It is a "knowledge divide", in which large sections of humanity are cut off not just from the information that could help them but from any learning system or community that fosters problem-solving. For instance, where people are dying of HIV/AIDS, tuberculosis (TB) or malaria despite the availability of technologies to control them, it is at least partly because the procedures for using those technologies effectively have not been worked out and learnt locally. Conversely, if scientists, administrators and technicians fail to stop the rise of these diseases in spite of big investments, detailed calculations and good intentions, it is at least partly because they do not know enough about how things actually work locally. Not only do health data tend to be more scarce in the places that have the more serious health problems, but there are fewer systems there for using even the data that are available to solve those problems. The result is failure to make the transition from information to action in the form, for example, of new treatment guidelines or government policy. The discipline of knowledge management (KM) aims to bridge this gap. Starting with the premise that local problems must have local solutions, effective KM in health can provide on an equitable basis the knowledge necessary for local innovation, and then produce new local knowledge that is in turn fed back and shared in a dynamic regenerative process. Although much of the content of KM is often perceived as information technology (IT), it goes in practice beyond the facilitating power of any single IT tool. Used in the way it should be, it harnesses experience through collaboration in direct, humanly interactive problem-solving. Two examples can give some idea of how this works. In the first, two nongovernmental organizations, Partners in Health and the Institute for Healthcare Improvement, have been working with the Peruvian Ministry of Health to improve TB treatment in that country. Last year they set up a pilot programme involving 41 clinics, using business software to link the clinics with a global team of TB experts, thereby forming a specific community of practice for solving problems, sharing innovations and gathering evidence. …
 
Article
This report deals with the geographical distribution, prevalence, epidemiology, etiology, serological, clinical, and histopathological features, and treatment of mal del pinto, or pinta, in Mexico.Repository penicillin preparations (PAM and Panbiotic) have been found highly effective in the treatment of this endemic, non-venereal treponematosis.
 
DISTRIBUTION OF 3301 PERSONS ADMITTED TO THE DENTAL COLLEGE, LUCKNOW, AND REPORTED TO BE USERS OF TOBACCO, BETEL NUT OR BOTH, ACCORDING TO SEX AND AGE 
DISTRIBUTION OF STUDY POPULATION ACCORDING TO SMOKING AND CHEWING HABITS AND ORAL LEUKOPLAKIA 
Article
Oral carcinoma has been shown to be correlated with the use of tobacco in various parts of India. In a large-scale dental survey conducted in Lucknow, Bombay and Bangalore various precancerous conditions were investigated and studied for their possible relation to smoking and chewing habits. This paper reports the prevalence of oral leukoplakia among 10 000 dental-clinic patients in Lucknow and the correlation of the condition with the use of tobacco and betel nut in the study population.The results show that leukoplakia is far more prevalent among users of tobacco, betel nut or both than among non-users. A strikingly high frequency was found among smokers of the local cigarette, the bidi.
 
Article
To quantify long-term health service use (HSU) following non-fatal injury in adults. A retrospective, population-based, matched cohort study identified an inception cohort (1988-91) of injured people who had been hospitalized (ICD-9-CM 800-995) aged 18-64 years (n = 21 032) and a matched non-injured comparison group (n = 21 032) from linked administrative data from Manitoba, Canada. HSU data (on hospitalizations, cumulative length of stay, physician claims and placements in extended care services) were obtained for the 12 months before and 10 years after the injury. Negative binomial and Poisson regressions were used to quantify associations between injury and long-term HSU. Statistically significant differences in the rates of HSU existed between the injured and non-injured cohorts for the pre-injury year and every year of the follow-up period. After controlling for pre-injury HSU, the attributable risk percentage indicated that 38.7% of all post-injury hospitalizations (n = 25 183), 68.9% of all years spent in hospital (n = 1031), 21.9% of physician claims (n = 269 318) and 77.1% of the care home placements (n = 189) in the injured cohort could be attributed to being injured. Many people who survive the initial period following injury, face long periods of inpatient care (and frequent readmissions), high levels of contact with physicians and an increased risk of premature placement in institutional care. Population estimates of the burden of injury could be refined by including long-term non-fatal health consequences and controlling for the effect of pre-injury comorbidity.
 
SERUM CONCENTRATIONS FOLLOWING INTRAMUSCULAR INJECTIONS OF PRODUCT A Patient Serum concentration (lU/mI) 
DAILY SERUM CONCENTRATIONS 
DATA FOR STUDENT'S t TEST ON PRODUCTS A AND B 
RE-TREATMENT RATES 
Article
In view of evidence suggesting that 1.2 mega-units of "all-purpose" penicillin (300 000 IU potassium penicillin G, 300 000 IU procaine penicillin G and 600 000 IU benzathine penicillin) did not maintain treponemicidal serum concentrations during the week following injection-which if true, might necessitate a reappraisal of prophylactic and treatment schedules in wide use against syphilis-daily assays were performed to determine the penicillinaemia levels in ambulant adult males for one week following intramuscular injection with this dosage of two "all-purpose" products (168 assays in all, 24 each day).Statistical evaluation of the results showed that the mean daily serum concentrations were, in fact, treponemicidal during the whole week after injection. The means of groups of 24 assays fell within narrow daily ranges on each of the seven post-injection days, suggesting that the long-acting component (benzathine penicillin) gives reliable and predictable daily levels in a high proportion of cases. This is in contrast to those penicillins which rely for their long-acting property on the oily gel in which they are suspended. On the other hand, the extremes of penicillinaemia for any individual in a large group were shown to cover a very wide range, demonstrating that a particular patient's failure to respond to standard treatment or prophylaxis can be due to factors quite unrelated to the quality or specificity of the product or to the sensitivity of the organism causing disease.
 
Article
As part of a WHO collaborative programme the prevalence of anaemia was studied and the serum concentrations of iron, folate, and vitamin B(12) were measured in 1 000 pregnant women from southern India. The results of the study show a high prevalence of anaemia, resulting from iron and folate deficiency with iron deficiency predominating. Interrelationships between these nutrients and their effect on pregnancy and the fetus were investigated. The results indicate that, in comparison with populations in developed countries, there was a high prevalence of iron and vitamin B(12) deficiency in the community, but the state of folate nutrition was similar to that found elsewhere.
 
Reactogenicity after ingestion of CVD 103-HgR live oral cholera vaccine or placeboa 
Seroconversion following immunization with a single dose of CVD 103-HgR live oral cholera vaccine 
Article
Despite considerable experience with single-dose, live, oral cholera vaccine CVD 103-HgR in Asia, Europe, and the Americas, the vaccine had not been evaluated in sub-Saharan Africa or on individuals infected with human immunodeficiency virus (HIV). We therefore conducted a randomized, placebo-controlled, double-blind, cross-over clinical trial in 38 HIV-seropositive (without clinical acquired immunodeficiency syndrome (AIDS)) and 387 HIV-seronegative adults in Mali to assess its safety and immunogenicity. Adverse reactions (fever, diarrhoea and vomiting) were observed with similar frequency among vaccine and placebo recipients. The vaccine strain was not isolated from the coprocultures of any subject. The baseline geometric mean titre (GMT) of serum vibriocidal antibody was significantly lower in HIV-seropositives (1:23) than in HIV-seronegatives (1:65) (P = 0.002). Significant rises in vibriocidal antibody were observed in 71% of HIV-seronegatives and 58% of HIV-seropositives, and in 40% of HIV-seropositives with CD4+ counts below 500 per microliter. Following immunization, the peak vibriocidal GMT in HIV-seronegatives was 1:584 versus 1:124 in HIV-seropositives (P = 0.0006); in HIV-seropositives with CD4+ counts < 500 per microliter, the peak vibriocidal GMT was 1:40 (P = 0.03 versus other HIV-seropositives). CVD 103-HgR was safe in HIV-infected Malian adults, although serological responses were significantly attenuated among HIV-seropositives (particularly in those with CD4+ counts < 500 per microliter) relative to HIV-seronegatives. These results encourage further evaluations of this single-dose, oral cholera vaccine in high-risk populations such as refugees in sub-Saharan Africa.
 
Estimated regional intake of fruit and vegetables 
Article
We estimated the global burden of disease attributable to low consumption of fruit and vegetables, an increasingly recognized risk factor for cardiovascular disease and cancer, and compared its impact with that of other major risk factors for disease. The burden of disease attributable to suboptimal intake of fruit and vegetables was estimated using information on fruit and vegetable consumption in the population, and on its association with six health outcomes (ischaemic heart disease, stroke, stomach, oesophageal, colorectal and lung cancer). Data from both sources were stratified by sex, age and by 14 geographical regions. The total worldwide mortality currently attributable to inadequate consumption of fruit and vegetables is estimated to be up to 2.635 million deaths per year. Increasing individual fruit and vegetable consumption to up to 600 g per day (the baseline of choice) could reduce the total worldwide burden of disease by 1.8%, and reduce the burden of ischaemic heart disease and ischaemic stroke by 31% and 19% respectively. For stomach, oesophageal, lung and colorectal cancer, the potential reductions were 19%, 20%, 12% and 2%, respectively. This study shows the potentially large impact that increasing fruit and vegetable intake could have in reducing many noncommunicable diseases. It highlights the need for much greater emphasis on dietary risk factors in public health policy in order to tackle the rise in noncommunicable diseases worldwide, and suggests that the proposed intersectoral WHO/FAO fruit and vegetable promotion initiative is a crucial component in any global diet strategy.
 
Percentage of groundwaters surveyed in 1998 by the British Geological Survey with arsenic levels over 50 mg/l 
Article
The contamination of groundwater by arsenic in Bangladesh is the largest poisoning of a population in history, with millions of people exposed. This paper describes the history of the discovery of arsenic in drinking-water in Bangladesh and recommends intervention strategies. Tube-wells were installed to provide "pure water" to prevent morbidity and mortality from gastrointestinal disease. The water from the millions of tube-wells that were installed was not tested for arsenic contamination. Studies in other countries where the population has had long-term exposure to arsenic in groundwater indicate that 1 in 10 people who drink water containing 500 micrograms of arsenic per litre may ultimately die from cancers caused by arsenic, including lung, bladder and skin cancers. The rapid allocation of funding and prompt expansion of current interventions to address this contamination should be facilitated. The fundamental intervention is the identification and provision of arsenic-free drinking water. Arsenic is rapidly excreted in urine, and for early or mild cases, no specific treatment is required. Community education and participation are essential to ensure that interventions are successful; these should be coupled with follow-up monitoring to confirm that exposure has ended. Taken together with the discovery of arsenic in groundwater in other countries, the experience in Bangladesh shows that groundwater sources throughout the world that are used for drinking-water should be tested for arsenic.
 
Article
Greenland experienced, during the 1950s, a decline in mortality such as is on record for hardly any other place in the world: from 24 per 1 000 in 1951 to 8 per 1 000 in 1960, a decline of more than 10% per year. Deaths from tuberculosis were especially reduced. Whereas more than one-third of all deaths in 1951 were considered to be due to this disease, practically no deaths are ascribed to it today.This rapid improvement in the health situation in Greenland, which coincides with a large-scale development programme, is documented in detail in the present paper. The study is based partly on official mortality statistics and partly on a 9-year follow-up study of mortality and of morbidity from tuberculosis in the total population of West Greenland registered in 1955. The existence of such data for a developing area is probably unique.
 
Article
Elimination of the onchocerciasis vector Simulium neavei through larvicidal operations in focal areas of Kenya in 1946, 1953, and 1955 achieved complete interruption of transmission. Since no treatment was administered to the infected population, the areas provided an opportunity for studying the natural course of the infection in man in the absence of reinfection, with particular emphasis on its average duration and the effect of duration of exposure to the infection. In a follow-up survey conducted in 1964 in four focal areas, approximately 2000 people were examined parasitologically and clinically; slightly over half this group were also given a thorough ophthalmological examination. The results showed that, 11 years after interruption of transmission, live Onchocerca volvulus adults were present in nodules and microfilariae were present in the skin; after 18 years, however, microfilariae were no longer found in the skin. Assuming that in hyperendemic areas parasites are acquired until shortly before interruption of transmission, it can thus be postulated that O. volvulus worms lose their reproductive potentiality after 16 years or possibly earlier. A comparison of recent microfilarial rates with adjusted rates found in earlier surveys seems to indicate that the onchocercal infection, after interruption of transmission, follows a straight regression line, theoretically reaching zero after about 13-17 years.
 
Article
The severity of trachoma in endemic areas has, in general, a tendency to decrease as a consequence of control measures and gradual improvements in sanitation and living conditions. The number of mild cases seen where the disease is prevalent is thus increasing and it is becoming more difficult to establish a differential diagnosis in certain cases, and to determine the degree of endemicity of the disease in a given area or community.In order to ascertain whether available laboratory methods could contribute useful data from this point of view, a clinical and laboratory study was carried out on the school population of the island of Djerba, off the south coast of Tunisia, during the school year 1963-64.The ophthalmological findings confirmed that, notwithstanding the large-scale treatment campaigns which had been in operation for 10 years, trachoma was then still highly endemic in the island, but relatively mild.The laboratory studies included microscopical examination of conjunctival scrapings for inclusion bodies, complement-fixation tests on serum specimens and-on a subsample of the populations studied-attempts to isolate the trachoma agent. The results indicated that the tests are more likely to be positive when the clinical signs are more pronounced. In individual cases, laboratory tests can at best confirm an already established clinical diagnosis and contribute little to the differential diagnosis of borderline cases.However, this study also indicated that the laboratory tests may provide useful quantitative indications on the endemicity of the disease in a community or in an area, from the point of view of the density of the agent and of the response to its presence. The techniques used must obviously be uniform enough to allow for a comparison with results obtained elsewhere or at different times.
 
Article
In previously published studies, a number of BCG strains used in several production laboratories were compared in animal models. Liquid vaccines from the different strains were prepared in one laboratory with a uniform technique, the aim being to obtain uniform in vitro properties. In the studies reported here, such vaccines were compared by means of vaccinating children in India and Denmark and then measuring their post-vaccination skin lesions and tuberculin sensitivity. One strain induced delayed hypersensitivity strikingly weaker than that induced by any of the others, although the vaccine was in no way inferior in terms of exhaustive in vitro tests. Differences among the other strains were slight, although sometimes statistically significant. The implications of such differences are discussed.
 
Constant and coefficients of best-fit polynomial equationsa for the mean and SD of MUAC-for-age b 
MUAC-for-age reference data for boys aged 6-59 monthSa 
MUAC-for-age reference data for girls aged 6-59 monthSa 
Article
Low mid-upper-arm circumference (MUAC), determined on the basis of a fixed cut-off value, has commonly been used as a proxy for low weight-for-height (wasting). The use of a fixed cut-off value was based on the observation that MUAC showed small age- and sex-specific differences. However, in 1993, a WHO Expert Committee concluded that age independence is not reflected in the true pattern of mid-upper arm growth, recommended the use of MUAC-for-age, and presented age- and sex-specific MUAC reference data developed with observations obtained from a representative sample of children in the USA aged 6-59 months. In this article, we explain the methodology for the development of these data, present age- and sex-specific growth curves and tables and discuss the applications and limitations of MUAC as a nutritional indicator. To develop the reference data, estimates were first obtained for the mean and standard deviation of MUAC for each month of age using 7-month segmental regression equations; a 5th-degree and a 3rd-degree polynomial in age was then used to describe the mean and standard deviation, respectively, of MUAC-for age. These curves show important age-specific differences, and significant sex-specific differences for boys and girls < 24 months of age. Correct interpretation of MUAC with regard to nutritional status requires the use of MUAC-for-age reference data such as those presented here.
 
Resistance to lamivudine (3TC), didanosine (DDI) and efavirenz (EFV), ANRS 12103 trial, Bobo-Dioulasso, Burkina Faso, 2006-2007
12 months-evolution of HIV RNA (median and interquartile range), ANRS 12103 
Article
To assess 12-month survival, pharmacokinetics, immunologic and virologic efficacy, tolerance, compliance and drug resistance in HIV-infected children in Bobo-Dioulasso, Burkina Faso, receiving once-daily highly-active antiretroviral therapy as a combination of didanosine (DDI), lamivudine (3TC) and efavirenz (EFV). In the ANRS 12103 open phase II trial, HIV-infected children were examined at inclusion and monthly thereafter. CD4+ T-lymphocyte (CD4) count, plasma concentration of ribonucleic acid (RNA) of human immunodeficiency virus type 1 (HIV-1) and haematologic and biochemical parameters were measured at baseline and every trimester. HIV-1 resistance testing was performed in case of viral escape. Drug plasma concentrations were determined with high-performance liquid chromatography. From February 2006 to November 2007, 51 children (39% girls) with a mean age of 6.8 years were enrolled and treated for 12 months. At baseline, Z scores for mean weight-for-age and mean height-for-age were -2.01 and -2.12, respectively. Mean CD4% was 9.0. Median plasma HIV-1 RNA viral load was 5.51 log(10) copies per millilitre (cp/ml). Two children (3.9%) died and another 11 (22%) suffered 13 severe clinical events. At month 12, mean WAZ had improved by 0.63 (P < 0.001) and mean HAZ by 0.57 (P < 0.001). Mean CD4% had risen to 24 (P < 0.001). Viral load was below 300 RNA cp/ml in 81% of the children; HIV resistance mutations were detected in 11 (21.6%). The once-a-day combination of DDI + 3TC + EFV is an alternative first-line treatment for HIV-1-infected children. Dose adjustment should further improve efficacy.
 
Article
The paper presents clinical observations on 1 233 persons with smallpox who were admitted to the Infectious Diseases Hospital, Calcutta, in 1973. The disease was of the modified type in 53 patients (4.3%), the ordinary type in 717 (58.2%), the flat type in 249 (20.2%), and the haemorrhagic type in 214 (17.3%). The fatality of these types of smallpox was found to be 5.7%, 26.8%, 88.4%, and 98.1%, respectively, and the overall case fatality was 50.7%. The haemorrhagic type was found mainly among older patients and affected males more often than females. The vaccination status of 1 218 patients was known. Of these, 901 (73.9%) were unvaccinated and had a fatality rate of 53.4%, whereas the 317 (26.1%) vaccinated patients had a fatality rate of 36.5%. Among the 201 haemorrhagic cases, 145 patients were unvaccinated (16.09% of the total number unvaccinated) and 56 (17.67%) had been vaccinated. Of 34 patients vaccinated during the incubation period, 19 (41.1%) died, whereas of 18 patients who had been vaccinated after the onset of fever, but before the appearance of rash, 9 (50%) died.
 
Article
Tris (p-aminophenyl) carbonium (TAC) salts and certain antimonials have been shown to be more effective together against Schistosoma mansoni in mice than would be expected from the simple addition of their activities when given alone. Owing to the toxicity of antimonials, the therapeutic advantage of such synergistic effects would largely depend upon whether or not they occurred because the co-administration of TAC pamoate led to higher or more sustained levels of antimony in the blood or tissues. This study of the effect of TAC pamoate on the physiological disposition of (124)Sb was designed to give information on this important aspect.In general, co-administration of or pretreatment with TAC pamoate had no significant effect on the disposition of antimony. This indicates that the additive or synergistic effect of the two drugs against schistosomes is not due to higher or more sustained levels of antimony in the blood and tissues.
 
Distribution of housing characteristics in the study population, Montalvania, Minas Gerais State, 19958 Number/mean 
Proportion of positive serological tests for Trypanosoma cruzi in Montalvania, Minas Gerais State, 19958 
Trypanosoma cruzi prevalence, by age group, Montalvania, Minas Gerais State, 1987 and 1995 % prevalence in: 
Relative changes in Trypanosoma Montalvania, Minas Gerais State cruzi infection rates in 
Overall prevalence and relative reduction of Trypanosoma cruzi infection observed in Montalvania, Minas Gerais State, 1995 
Article
Reported is an evaluation of 13 years of intervention by the Chagas Disease Control Programme in an endemic area (Montalvania) in the State of Minas Gerais, Brazil. The design used was an epidemiological panel study. The reduction of Trypanosoma cruzi infection rates was estimated from data collected on three separate occasions: a serological survey in 1975-80, a quasi-experimental study in 1987, and the present investigation. A random sample of 156 households was selected and blood samples were collected from 653 inhabitants. The data routinely collected by the control programme were analysed to correlate the results with the incidence of T. cruzi. The overall prevalence of infection was 2.3%; however, no participant under 14 years of age was found to have a positive serological test. The total reduction in T. cruzi infection rates in this area from the start of the programme's activities was estimated to be 83.5%. Cross-sectional comparisons for the age groups 2-6 years and 7-14 years indicated a 100% reduction in T. cruzi incidence rates; but cohort comparisons showed that 100% reduction was achieved only for the 2-6-years age group.
 
Significant results in the multivariate analysis of Schistosoma mansoni Infection and reinfection 
Article
The incidences of Schistosoma mansoni infection and reinfection were investigated in an endemic area of Brazil (Peri-Peri, State of Minas Gerais) where chemotherapy and snail control had been used for 13 years (1974-87). Two cohorts were followed: the first consisted of 584 individuals with no evidence of infection at entry (infection cohort), and the second comprised 296 individuals who were treated and did not eliminate eggs 8-12 months afterwards (reinfection cohort). The incidence of infection (per 100 person-years) decreased from 7.5 in 1974-77 to 3.6 in 1986-87, and that of reinfection from 21.3 in 1974-77 to 3.7 in 1986-87. Calendar period, age at risk, and sex were independently associated with both infection and reinfection, while a heavy S. mansoni egg count prior to treatment (> or = 500 epg (eggs per gram of stools)) was independently associated with reinfection. The geometric mean number of eggs after treatment among those reinfected (47 epg) was approximately half that among those infected for the first time (81.5 epg). Age at risk had the greatest effect on both infection and reinfection. The rate ratios of infection and reinfection were 3 to 6 times higher among individuals younger than 20 years than among those aged > or = 25 years, even after adjusting for confounders. This suggests the existence of a strong protective effect with increased age (because of biological and/or environmental factors) for both infection and reinfection.
 
Total no. of outpatients seen annually in all hospitals and dispensaries, Sayaboury Province, Lao People's Democratic Republic, 1996-2003
Key health indicators in Sayaboury Province (2003) compared with national data from the Lao People's Democratic Republic (Lao PDR) (2002)
Article
The Lao People's Democratic Republic (Lao PDR) is classified by the World Bank as a low-income country under stress. Development partners have sought to utilize effective aid instruments to help countries classified in this way achieve the Millennium Development Goals; these aid instruments include sector-wide approaches (SWAps) that support decentralized district health systems and seek to avoid fragmentation and duplication. In Asia and the Pacific, only Bangladesh, Papua New Guinea and the Solomon Islands have adopted SWAps. Since 1991, a comprehensive primary health care programme in the remote Sayaboury Province of Lao PDR has focused on strengthening district health management, improving access to health facilities and responding to the most common causes of mortality and morbidity among women and children. Between 1996 and 2003, health-facility utilization tripled, and the proportion of households that have access to a facility increased to 92% compared with only 61% nationally. By 2003, infant and child mortality rates were less than one-third of the national rates. The maternal mortality ratio decreased by 50% despite comprehensive emergency obstetric care not being available in most district hospitals. These trends were achieved with an investment of approximately 4 million US dollars over 12 years (equivalent to US 1.00 US dollars per person per year). However, this project did not overcome weaknesses in some national disease-control programmes, especially the expanded programme on immunization, that require strong central management. In Lao PDR, which is not yet committed to using SWAps, tools developed in Sayaboury could help other district health offices assume greater planning responsibilities in the recently decentralized system. Development partners should balance their support for centrally managed disease-specific programmes with assistance to horizontally integrated primary health care at the district level.
 
Institutions selected for the two-year prospective study 
Types of adverse events in neonates receiving intradermal Copenhagen 1331 BCG vaccine 
Number of children with tuberculous meningitis and miliary tuberculosis at King George V Hospital, a tuberculosis isolation facility, before and after change of vaccination policy (July 1997) 
Visible vaccination status and frequency of adverse events associated with neonatal intradermal Copenhagen 1331 BCG vaccinations at different types of institutions 
Article
To evaluate the safety of the intradermal Copenhagen BCG vaccine in neonates at different levels of delivery and neonatal units of the Durban Functional Region and surrounding regions. A prospective study was carried out over a two-year period between July 1997 and June 1999. All neonates who had been vaccinated with the intradermal vaccine were evaluated at immunization clinics six weeks after immunization, or earlier if adverse effects occurred. In total, 9763 neonates were examined: in 95.4% the vaccination scar had healed and 1.5% had no visible scar. Adverse events occurred in 3.1%. The proportion of neonates with no visible vaccination scars decreased over the study period, as did the number with adverse events. The lowest rate of adverse events and the highest rates of healed vaccination scars were seen in the tertiary hospital and regional and district hospitals that were in close proximity to the academic centre involved in this study. In the study sites, the transition from the percutaneous to intradermal route of administration of BCG vaccine was successful and took place without incurring unacceptably high rates of adverse events. To minimize adverse events, however, it is essential to continue training health personnel involved in implementing intradermal BCG vaccination programmes.
 
Frequency distribution of trends in TB incidence rate in six groups of countries (n = 134), 1997-2006 a 
Trends in average TB incidence rate across six groups of countries (n = 134), 1997-2006 a 
Sanitation: a statistically significant correlate of trends in TB incidence rate across six groups of countries over 1997-2006, as determined by univariate linear regression (fitted line) a 
Article
To determine whether differences in national trends in tuberculosis incidence are attributable to the variable success of control programmes or to biological, social and economic factors. We used trends in case notifications as a measure of trends in incidence in 134 countries, from 1997 to 2006, and used regression analysis to explore the associations between these trends and 32 measures covering various aspects of development (1), the economy (6), the population (3), behavioural and biological risk factors (9), health services (6) and tuberculosis (TB) control (7). The TB incidence rate changed annually within a range of +/-10% over the study period in the 134 countries examined, and its average value declined in 93 countries. The rate was declining more quickly in countries that had a higher human development index, lower child mortality and access to improved sanitation. General development measures were also dominant explanatory variables within regions, though correlation with TB incidence trends varied geographically. The TB incidence rate was falling more quickly in countries with greater health expenditure (situated in central and eastern Europe and the eastern Mediterranean), high-income countries with lower immigration, and countries with lower child mortality and HIV infection rates (located in Latin America and the Caribbean). The intensity of TB control varied widely, and a possible causal link with TB incidence was found only in Latin America and the Caribbean, where the rate of detection of smear-positive cases showed a negative correlation with national incidence trends. Although TB control programmes have averted millions of deaths, their effects on transmission and incidence rates are not yet widely detectable.
 
Scheme for the clinical and epidemiological investigations of live, cold-adapted influenza vaccine
Frequency of febrile reactions among the study children who received live, cold-adapted influenza vaccine or placebo in three successive years
Effect on the functional action of lymphocytes of immunizing pre- school children with live, cold-adapted influenza vaccines Stimulation index for period:a
Immunogenicity of live, attenuated mono-and polyvalent cold-adapted influenza vaccines in children aged 5-14 years with initial titres of haemagglutination-inhibition (HI) antibody <1:20
Concentration of IgE in the sera of children vaccinated with live, cold-adapted influenza vaccines
Article
Reported is a study of live, cold-adapted (CA) reassortant mono-, di-, and trivalent influenza type A and B vaccines in a series of controlled clinical and epidemiological investigations involving nearly 130 000 children aged 3-15 years. The results of clinical, immunological, and morbidity investigations of the vaccinees and a control group over 6-months' follow-up indicated that the vaccines were completely attenuated by the children. Transient febrile reactions occurred in < 1% of the children after vaccination, including double seronegative individuals with low antibody titres. The type A reisolates examined were genetically stable. The reassortants did not suppress each other after simultaneous inoculation of children and stimulated antibody response to influenza virus strains A1, A3, and B. The incidence of influenza-like diseases was approximately 30-40% lower among the vaccinated group than among the control group. The study demonstrates, for the first time, the efficacy of CA vaccine against infections caused by influenza B virus.
 
Article
Vector resistance and other constraints have necessitated consideration of the use of alternative materials and methods in an integrated approach to vector control. Bacillus thuringiensis serotype H-14 is a promising biological control agent which acts as a conventional larvicide through its delta-endotoxin (active ingredient) and which now has to be suitably formulated for application in vector breeding habitats. The active ingredient in the formulations has so far not been chemically characterized or quantified and therefore recourse has to be taken to a bioassay method. Drawing on past experience and through the assistance mainly of various collaborating centres, the World Health Organization has standardized a bioassay method (described in the Annex), which gives consistent and reproducible results. The method permits the determination of the potency of a B.t. H-14 preparation through comparison with a standard powder. The universal adoption of the standardized bioassay method will ensure comparability of the results of different investigators.
 
Article
In 55 villages from the well-protected central area of the Onchocerciasis Control Programme in West Africa (OCP), skin snip surveys have been carried out at regular intervals since the programme started, and the latest round of surveys was undertaken after 12-14 years of successful vector control. The observed trends in the prevalence and intensity of onchocerciasis infection in cohorts of adults were compared with the trends predicted using a host-parasite model. After 12-14 years of control the community microfilarial load (CMFL) was close to zero in all villages. During the last few years of control, the prevalence of infection declined at an accelerated rate, and this was predicted by the model. There was generally good agreement between observed and predicted trends. The predictions were based on an estimated average duration of infection of 10.4 years, which corresponds to a mean reproductive lifespan for Onchocerca volvulus of 9-9.5 years, and an upper limit of 15 years for 95% of the infections. Differences between the observed and predicted data included the trend in CMFL between the first and second surveys, which in 18 villages did not show the predicted decline. Furthermore, the observed final decline in prevalence was faster than predicted in the north-eastern part of the central OCP area. After 14 years of vector control, the level of onchocerciasis has fallen to such a low level that consideration is being given to ending larviciding.
 
Article
A serological survey of antibodies to influenza A(H1N1), A(H2N2), A(H3N2) and B viruses was done with sera collected in Moscow in October 1980 and November 1981 from 542 children under 14 years of age. The results of the study showed convincingly that influenza A(H2N2) viruses were not circulating in Moscow in 1980-81. Low titres found in the sera from four young children were due to cross-reactions which were eliminated from the sera by absorption with A/USSR/174/79(H3N2) virus. Low-level HI titres with A(H0N1) virus in 11 sera were not confirmed by single radial haemolysis (SRH).Serological data showed that A(H3N2) viruses were the main cause of acute respiratory disease in children in July-September 1980 and July-September 1981. These illnesses occurred at the end of the influenza A(H3N2) epidemic of 1979-80 in the third quarter of 1980. The influenza A(H3N2) virus circulated in Moscow during December 1981 and January 1982, but influenza did not reach epidemic levels. A low proportion (10%) of children with antibodies to influenza B virus at titres of 1:40 or higher in 1980 indicated the possibility of an epidemic due to this virus in Moscow in 1980-81. Such an epidemic did occur in December 1980 and January 1981.
 
Pathogens identified in 140 patients with fatal diarrhoeal diseases 
Age and sex distribution of 140 patients with fatal diarrhoeal diseases who underwent autopsies compared with all the patients who died in the same hospital in the same period 
Article
The cause of death (besides dehydration) for 140 diarrhoeal patients who died in hospital following rehydration was determined by autopsy examination. Children under 5 years comprised 74% of the patients. Diarrhoeal pathogens were identified as Shigella spp. in 27%, enterotoxigenic Escherichia coli in 17%, Entamoeba histolytica in 16%, Campylobacter jejuni in 12%, Salmonella spp. in 4%, Vibrio cholerae in 4%, and Giardia lambliain 4% of cases. The most frequent underlying causes of death were colitis in 44% and pneumonia in 38%. The most frequent immediate causes of death were septicaemia in 27%, hypoglycaemia in 9%, and hypokalaemia in 9%; multiple causes of death were present in 89% of cases. Kwashiorkor or marasmus was present in 59% and fatty degeneration of the liver was detected in 61% of cases. It is concluded that, in susceptible children, diarrhoeal pathogens produce destructive inflammation in the intestine and cause death or contribute to it by provoking disease in other tissues, especially septicaemia and fatty liver, or by combining these effects with antecedent or concomitant conditions, especially pneumonia and malnutrition.
 
Article
In preliminary studies with mefloquine (WR 142 490) a single dose exerted prolonged suppressive activity against a drug-resistant strain of Plasmodium falciparum. Development of patent parasitaemia was prevented when nonimmune persons were exposed to infected mosquitos 2 weeks after medication, and it was delayed when exposure occurred 3 weeks after drug administration.
 
Article
PIP The results of 16 years' prophylaxis against endemic goiter among children in Tasmania are given. A survey carried out in 1949 showed a relatively high prevalence of endemic goiter among children in most parts of the island, and in 1950, distribution of tablets containing 10 mg of potassium iodide to all school children was commenced. This distribution was gradually stopped during 1966 as legislation made it possible to add potassium iodate to all bread baked on the island. Periodic surveys showed that the prevalence of endemic goiter has fallen significantly but has not vanished entirely. Seasonal fluctuations in the prevalence found in some regions of the island decreased at the same time. Histopathological studies on goitrous tissue and iodine estimations on body fluids confirmed that the goiter in Tasmania is typical of endemic goiter, which is usually attributed to iodine deficiency. The effect of the treatment of established goiters in adolescent girls with thyroxine is described, as are results of the studies of the ability to taste phenylthiocarbamide, a property which may be genetically linked to a predisposition to goiter. (author's) (summary in ENG).
 
Article
This study is another in the WHO series of comparisons of measles vaccines prepared from different strains of virus. The Leningrad-16 strain was compared with the Schwarz strain in a trial with children aged 1 to 6 years. A group inoculated with placebo was included as a control.Pyrexias and rashes were more common in the Leningrad-16 group than in the Schwarz group but in neither were the reactions serious. Antibody responses were good in both groups.During the 12 months after vaccination, measles occurred in 5% of the children known to have been exposed to infection in the Leningrad-16 group, 6% in the Schwarz group and 58% in the control group.
 
Article
During the period 1958-73, 8 027 strains of Salmonella were tested at the National Salmonella and Escherichia Centre: 3 834 strains from man, 3 018 from animals, 839 from sewage and water sources, and 336 of unknown origin. A total of 99 serotypes were identified: 47 from man, 83 from animals, and 35 from sewage and water sources. S. typhi was the commonest serotype in man, followed by S. weltevreden and S. paratyphi A. S. typhimurium was the commonest serotype isolated from animals, followed by S. weltevreden and S. anatum. In sewage and other water sources S. weltevreden was the commonest serotype identified followed by S. typhimurium and S. bareilly. Infection due to S. weltevreden in both man and animals increased considerably after 1970. Out of a total of 99 serotypes isolated from different sources, 13 were isolated from man only, 49 from animals only, 34 from both man and animals, 30 from both animals and water sources, and 22 from man, animals, and water sources.
 
Article
In this paper an analysis of genetic recombinants derived from crosses between two mutant stocks of Vibrio cholerae, strain 162, differing from one another in nutritional requirements and other characters, is presented. It is shown that parent strains possessing a fertility factor (designated as the P factor) function as gene-donors while P(-) strains (without the P factor) serve as gene-recipients. Linkage between two genetic factors (purine and valine + isoleucine) is demonstrated and the probable sequence of seven genetic factors in the chromosome of V. cholerae, strain 162, is inferred.
 
Article
A live dengue-2 (DEN-2) candidate vaccine (strain 16681-PDK 53), attenuated by passage in primary dog kidney cells, was tested in ten adult volunteers for evaluation of the safety, infectivity and immunogenicity of a dose of 1.9-2.7 x 10(4) plaque-forming units. Five of the volunteers were nonimmune to either dengue or Japanese encephalitis (JE) viruses; the other five were nonimmune to dengue but immune to JE. After receiving 1.0 ml of the vaccine subcutaneously, all ten volunteers developed neutralizing antibodies to DEN-2 which were maintained for at least one and a half years. None of the subjects developed abnormal signs or symptoms and the results of clinical chemistry investigations were within normal range throughout the 21 days of observation after the immunization. Virus isolated from one viraemic volunteer retained the small-plaque and temperature-sensitive growth characteristics of the vaccine virus in vitro. Further testing of this candidate vaccine in humans is indicated.
 
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Silvio Paolo Mariotti
  • World Health Organization WHO
Serge Resnikoff
  • UNSW Sydney
Ivo Kocur
  • World Health Organization WHO
Chizuru Nishida
  • World Health Organization WHO
Jonathan Siekmann
  • City College of San Francisco