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The effect of a 14-valent pneumococcal polysaccharide vaccine on morbidity from acute lower respiratory tract infection (ALRI) was determined in a randomized double-blind controlled trial in children under the age of 5 years living in the Paupa New Guinea highlands. The vaccine did not protect against mild ALRI. Vaccine efficacy in the study as a whole was 28% for moderate/severe ALRI, which was not statistically significant though consistent with the significant effect on mortality. Children entered the trial in five separate cohorts 4 months apart. The incidence of disease and vaccine efficacy varied between cohorts and with age. There was no vaccine effect in the first cohort, which had a much higher proportion of older children. The effect was greatest and statistically significant among those groups encountering an epidemic of moderate and severe ALRI at a young age. It was therefore in children at the most vulnerable age in times of greatest incidence of disease that the vaccine had its most potent effect. It is postulated that the efficacy of pneumococcal vaccine is dependent on the predominant invading serotypes in the period after vaccination, the age at which children develop immunocompetence to specific vaccine serotypes, and the levels of naturally acquired specific immunity already present in children at the time of vaccination, and that for all of these conditions there will be a cohort effect.

The possible role of pigs as arbovirus maintenance hosts and their importance as amplifier hosts was studied. Blood samples from 464 pigs of all ages collected in 1962 and 1964 were tested against 10 arboviruses. Antibodies to Japanese encephalitis and Getah viruses were particularly prevalent and their calculated monthly infection rates were 19-5% and 13-3% respectively. In 1969, 447 pigs were bled monthly throughout the year and the infection rates for Japanese encephalitis virus were calculated in pigs during the first year of life. Infection rates were not uniform throughout the year; the rate increases as the pig grew older and there was a marked seasonal increase in the infection rate in the period from November to January. This coincided with the seasonal major population peak of Culex tritaeniorhynchus following intense breeding of this mosquito prior to rice planting. It is suggested that, in Sarawak, the pig acts as a maintenance host of Japanese encephalitis in a cycle involving C. gelidus mosquitoes and also acts as an important amplifier host towards the end of the year in a cycle involving C. tritaeniorhynchus. It is further suggested that Getah virus is maintained in a similar cycle between C. tritaeniorhynchus and pigs.

After an interval of four years the same observers used the same standardized techniques to re-examine 1,016 people in 12 heavily infected rain-forest and savanna villages in Cameroon. The changes in the number of nodules and in the concentration of microfilariae in the skin and eye are described. These latter changes are correlated with the development and/or deterioration of eye lesions and visual impairment. In both the rain-forest and the savanna there was a strong association between the development of eye lesions and a high concentration of microfilariae, not only in the eye but also in the skin, and more so at the shoulder than at the buttock. The importance of these findings for the prevention of blindness is discussed.

The antibody response to group C meningococcal polysaccharide vaccine was studied in a Nigerian village. Household clustering of poor responders to immunization was detected. Age had a marked effect on antibody response, maximal titres being obtained only in those over the age of 10 years. Children with malaria parasitaemia had a lower antibody response than those without parasitaemia and subjects with the genotype AA had a lower antibody response than those with the genotype AS. The antibody response to the vaccine was not influenced by mild degrees of malnutrition but children with clinical marasmus or kwashiorkor were excluded from the study.

Simultaneous xenodiagnosis was made of 29 patients with chronic Chagas's disease, six naturally infected opossums ( Didelphis azarae ) and of a Rhesus monkey with an experimental chronic infection with Trypanosoma (Schizotrypanum) cruzi (Peru strain). Patients and opossums were from an endemic area in the state of Bahia, Brazil, where Panstrongylus megistus is the sole domiciliary vector of the disease to man. Various instars of P. megistus Triatoma infestans and Rhodnius prolixus were used. The proportion of bugs infected was compared with bloodmeal intake by a computer programme using linear logistic analysis. The analysis showed that there are intrinsic interspecific differences in susceptibility to infection with Trypanosoma cruzi between the three triatomine species used and that subsequent infection of bugs with T. cruzi is correlated with the quantity of blood ingested. The results show that interspecific differences of bloodmeal size and intrinsic differences in susceptibility to T. cruzi between triatomine species are limiting factors for the standardization and interpretation of the results of xenodiagnosis.

SummaryFourteen 9-month-old zebu calves were immunized with 10000 irradiatedSchistosoma bovisschistosomula given in 1–3 intramuscular or subcutaneous doses, and 4 more calves were immunized with 10000 irradiated cercariae administered percutaneously in a single dose. Eight weeks after the beginning of the experiment these calves, together with four non-immunized controls were challenged percutaneously with 10000 normalS. boviscercariae/calf. Comparative clinical, parasitological, pathological and pathophysiological observations subsequently revealed significant differences between the vaccinated and non-vaccinated calves. The vaccinated calves showed significantly higher growth rates, and a superior body composition as indicated by their lower total body water content. The beneficial effects of vaccination were also shown by significantly lower faecal egg outputs in the vaccinated calves and by their lower tissue egg and adult worm counts. The reduced tissue egg counts were also reflected in the milder histopathological changes seen in the vaccinated calves. The vaccinated calves had significantly higher packed cell and circulating red blood cell volumes than the challenged controls, longer red blood cell half lives, and somewhat lower blood volumes and rates of red blood cell synthesis. No untoward clinical effects that could be attributed to vaccination were recorded. These results indicate that zebu cattle can be effectively protected againstS. bovisby vaccination with irradiated organisms. We are now evaluating this type of vaccine in a field trial in an enzootic area in the Sudan.

Age-specific prevalence rates of antibody to O'nyong-nyong virus were determined in samples of the population in the Kano Plain, near Kisumu, and Bunyala. Presented graphically, the rates show a cl...

In three double-blind placebo-controlled trials of pneumococcal capsular polysaccharide vaccines against death from acute lower-respiratory-tract infections (ALRI), children were vaccinated at 6 months to 5 years of age. The efficacy of the vaccines against ALRI as the sole cause of death was estimated at 59% in children vaccinated when younger than 5 years (p=0·008) and 50% in children vaccinated when younger than 2 years (p=0·043). Mortality from all causes was 19% less in the vaccinated group.

The control of the snail vectors of schistosomiasis by aerial application of the molluscicide N-trityl morpholine was carried out in a 80 000 ha area from 1974 to 1977. The effect of this molluscicide regimen on transmission of Schistosoma mansoni was monitored by longitudinal surveys in a number of schools and in pre-school-age children. A cross-sectional school survey was carried out in 1977.There was no significant difference in incidence between the treated area and an adjacent untreated area as measured by the longitudinal school survey, the longitudinal village survey, or the cross-sectional survey. Consideration of egg output and prevalence (as determined by ELISA test) also failed to reveal any difference between the two areas.The initial prevalence and intensity in the subjects selected from the treated area were higher than in the untreated area, and some villages showed possible transmission reduction. In general, however, the results showed a great variation in infection rates and intensity wi...

SUMMARYThis paper describes further characteristics of the immunization of sheep against schistosomes using live, irradiated schistosomula. Sheep immunized with a non-virulent strain of Schistosoma mattheei were protected against a more virulent strain of the same species for over a year. As there was no evidence that the irradiated parasites were able to persist this long, it was concluded that the vaccine had induced a sterile resistance. Heterologous vaccination, using irradiated S. mattheei schistosomula to immunize against S. bovis or irradiated S. mansoni schistosomula to immunize against S. mattheei, failed to induce any protection.

The results of an onchocerciasis survey of total populations aged 5 years and over in 16 heavily infected villages in Cameroon rain-forest and savanna zones are reported. Using standardized parasitological and clinical techniques the same observers examined the intensity of infection and clinical manifestations in 1,098 cases in the rain-forest and compared them with those found in 1,128 cases in the savanna. The following Table summarizes the main findings:- Rainforest Savana Prevalence of nodules 80–90% 60–70% Mean number of nodules per person +++ ++ Microfilarial skin density ++ −++ Skin atrophy ++ +++ Shin depigmentation +++ + Groin lymphadenopathy +++ ++ Hanging groin ++ + Microfilarial invasion of cornea ++ +++ Microfilarial invasion of anterior chmaber +++ +++ Microfilarial invasion of vitreous + ++ Snowflake corneal opacities ++ + Sclerosing keratitis + +++ Iritis + +++ Optic atrophy + + Choroidoretinitis + + Blindness 2.0% 5.1% + =at low level ++ =at medium level +++ at high level It is suggested that the differences between rain-forest and savanna may be due to variations in host response resulting from differences in the intensity and patterns of transmission. Different pathogenicity of the rain-forest and savanna strains of parasite is also considered to be of importance, and it is suggested that concomitant infections may influence the immunological response. Hormonal factors are considered to be important in influencing the differences in the patterns and severity of infections between males and females.

Cette etude confirme l'importance des bacteries dans l'etiologie et la pathogenie des infections aigues graves des voies respiratoires inferieures en Paponasie Nouvelle-Guinee. La bacteriemie quintuple presque le risque de deces. Homophilus influenzae et S. pneumoniae sont predominantes

Laboratory observations were made on the transmission of Wuchereria bancrofti by Culex quinquefasciatus and Anopheles gambiae, natural vectors in East Africa, and by Aedes aegypti, an experimental vector. Mosquitoes were fed on human carriers with one to 2,667 microfilariae (mff/ml) of peripheral blood and the numbers of mff ingested were determined. The mosquitoes demonstrated a ‘concentrating effect’ and ingested 8.6 to 12-fold more mff than the expected number based on the density of mff in the carrier and the size of the blood meal. Studies on Culex showed that only 2.7 to 13% of the ingested mff developed into infective larvae (L3s). Emphasis was given to the transmission of Wuchereria from low density carriers with less than 10 mff/ml of peripheral blood—a value that approximates the threshold level of microfilaraemia detectable with conventional diagnostic techniques. By combining our laboratory data with published field data on the biting rates and longevity of mosquitoes in East Africa, we estimate that each low density carrier could serve as a source for nil to 15 L3s/year in Cx quinquefasciatus and 0.3 to 8 L3s/year in An. gambiae depending on the particular community. These estimates are relevant when formulating strategy to control bancroftian filariasis by mass chemotherapy with diethylcarbamazine. Experience with this drug has shown that a proportion of the carriers in a community continue to circulate mff at low levels after treatment. The present data demonstrate that these carriers serve as a reservoir of infection for mosquitoes.

The experiment described was conducted in water impounded by earth dams, for local water-supply, in Nyanza province, Kenya. Control of snails was attempted by introduction of the malacophagous fish Astatoreochromis alluaudi; other species were also introduced. The schedules of introduction of fish were varied between the reservoirs, and one was left as a control without any introduction of fish. The necessity for the establishment of a fish-rearing pond, prior to large-scale stocking, is emphasized.Assessment of snail control was made by scooping for snails, catches being expressed per man-hour. This was carried out both before and after introduction of fish, over a total period of 15 years. It is concluded that the data indicate that A. alluaudi did reduce the numbers of some species of snails—particularly Biomphalaria pfeifferi and, to a lesser extent and with less certainty, Bulinus spp.Two other introduced fish species, Tilapia zillii and T. leucosticta, did not appear to be associated with any fall in snail numbers.

A study of morbidity in Schistosoma mansoni infection was made in 593 Sudanese patients seen in a four-year period in Khartoum Civil Hospital. Clinical and laboratory findings were compared in three egg-count groups and in four clinical forms of the infection. Patients were divided into three levels of intensity of infection: light (up to 100 eggs/gram of stool), moderate (101--400 eggs/g) and heavy (more than 400 eggs/g). According to the presence or absence of visceral enlargement, infected subjects were divided into one of four clinical forms: intestinal, hepatic, hepatosplenic and splenic. Among the symptoms only the passage of blood in the stools was significantly related to intensity of infection, and fever was significantly related to the presence of hepatosplenic disease. Hepatomegaly and splenomegaly were significantly more frequent in the heavy infection group. Anaemia, eosinophilia, raised ESR and an increase in both serum alkaline phosphatase and serum globulins were significantly related to the intensity of infection. On the other hand, haematological and biochemical changes, as well as histopathological changes, were more marked and severe in patients with hepatosplenic disease. For comparison, the findings of 117 patients with S. haematobium infections and of 41 with dual S. mansoni/S. haematobium infections are included.

Evidence is presented that female Anopheles farauti Laveran released in an alien village dispersed more, in their first oviposition cycle after release, than females released in their village of capture. In a subsidiary experiment transporting the mosquitoes did not affect dispersal; wind speed or direction was not sufficient to account for the phenomenon. It is hypothesized that these permanent-pool breeding mosquitoes make appetitive long-range flights to oviposition sites. Mosquitoes blood-fed before midnight had a shorter oviposition cycle than those fed just before dawn. Nulliparous females, and those with well-defined ovariolar dilatations, predominated in the early evening whereas females that had oviposited recently were largely collected in the middle and later parts of the night.

During a three-year period of effective control of Schistosoma haematobium transmission by molluscicide application the mean number of S. haematobium ova passed by subjects in the treated area fell in an exponential manner which suggested that the mean life span of the worm was 3·4 years. Parallel observations were made in a similar but untreated area. A comparison of the observations in these two areas suggested that in the untreated area subjects of all ages acquired infection during the course of the study. At the end of the study over 50% of the egg output in most age groups in the untreated area appeared to come from worms acquired during the preceding three years. There were substantial differences between age groups in the amount of infection acquired. Children, aged between eight and ten years at the end of the study, appeared to be passing perhaps a thousand times more ova from worms acquired during the preceding three years than were middle-aged subjects. Preliminary observations suggest that age- and sex-related differences in the pattern of water contact may not fully account for age- and sex-related differences in the rate of acquisition of infection and its prevalence. The probable significance of protective immunity in the epidemiology of schistosome infections is discussed.

The roles of some of the factors thought to be responsible for the characteristic relationship between age and the intensity and prevalence of Schistosoma haematobium infection have been investigated. In this initial report a study population in an area of intense infection is described, as are the methods used. Subsequent papers report the effect of interrupting transmission with molluscicide in part of the area and compare changes in egg count in this treated area with changes in an area where no intervention took place. These allow a consideration of age-specific rates of loss and acquisition of infection to be made. The intensity and prevalence of infection varied between villages both in the treated and untreated areas, but the relation of age to the pattern of infection was regardless of the level of infection in the villages. Over-all, the number of subjects and their pattern of infection was similar in both areas. The prevalence of infection tended to be higher in adult males than females but preliminary water contact observations suggest males are less exposed to infection. Observations over the three-year study period emphasize the extent of population movement in the study area and point to its importance in the planning of control measures.

Publisher Summary The subgenus Trypanozoon contains several kinds of trypanosome, which are morphologically indistinguishable but differ in their behavior. At various times specific or subspecific status has been accorded to each kind, but, in recent years, those cyclically transmitted by tsetse in Africa have been separated into subspecies of Trypanosoma brucei , while the others, transmitted non-cyclically outside the African tsetse belts, have retained separate species status. However, although such new terminology may be more correct taxonomically, the practical problems of distinguishing the trypanosomes remain. Enzyme electrophoresis is being used on an increasingly wide scale for the intrinsic characterization. However, as the number of enzyme systems being used for identification grows, comparison of stocks becomes increasingly difficult and intricate, particularly when an enzyme occurs in a multibanded form after electrophoresis. After using 12 enzyme systems to characterize 160 Trypanozoon stocks, the results have been analyzed to establish the degree of relatedness of each of the 59 zymodemest encountered. The detailed analysis is presented in this chapter.

A cross sectional study of schistosomiasis in migrant labourers in the Sudan Gezira is described. The people examined were of two ethnic groups: (i) those of local Arabic origin and (ii) those from Western Sudan, West Africa or west of longitude 27 °E. These two migrant groups were examined in one area treated with molluscicide and in another that was not. Almost all the schistosome infections were with Schistosoma mansoni , with a prevalence of 57% over-all and up to 89% in particular groups. The prevalence was lower in the treated than in the untreated area, and slightly lower in the Arab nomads than in the others, except that it was markedly lower in females from the West in the treated area. These results are consistent with the known water-contact habits of the two migrant groups. An association was observed between infection and liver and spleen enlargement, but not between infection and other symptoms. The potential importance of migrants in transmitting the infection is discussed.

Results of xenodiagnosis and haemoculture of 44 different animal and human subjects were compared quantitatively by linear logistic analysis. Both diagnostic methods were carried out simultaneously on each test subject: results of xenodiagnosis and haemoculture were compared among the following groups of subjects: (i) 14 laboratory mice with chronic experimental infections of Trypanosoma cruzi (Bahia isolates); (ii) eight opossums ( Didelphis azarae ) naturally infected in Bahia, Brazil; (iii) six patients in the acute stage of Chagas's disease; (iv) 16 patients in the chronic inapparent stage. For xenodiagnosis of the different subjects fifth-instar Rhodnius prolixus , first-instar and fourth or fifth-instar Panstrongylus megistus , and fifth-instar Triatoma infestans were used. The number of each species and instar used in xenodiagnosis varied between five and 40 on each subject: mean intake of blood by batches of bugs was obtained by weighing each group before and after feeding. Whilst xenodiagnosis was carried out, each subject was bled and 1 to 2 ml of blood inoculated into two to nine tubes of culture media, most frequently Warren's medium, but in some instances 4N medium. Quantities of 0·1 to 0·2 ml blood were inoculated into each 5 ml of culture media. Cultures were incubated at ambient temperature (23 °-28 °C) and observations of primary cultures were continued fortnightly up to six months post-inoculation. The detailed results were subjected to statistical analysis and are discussed and compared with those obtained by other workers. Aspects of both xenodiagnosis and haemoculture are discussed, with particular reference to the fact that most previous workers have found xenodiagnosis superior to haemoculture in the diagnosis of chronic T. cruzi infections. It is concluded that, in principle, haemoculture is no less sensitive than xenodiagnosis in the diagnosis of chronic infections, and that indeed haemoculture has several advantages, particularly in regard to potential future improvement and standardization of techniques. Cultural methods require further refinement in order to make haemoculture a practicable alternative method for routine diagnosis.

Niclosamide was used to interrupt transmission of Schistosoma haematobium by Bulinus senegalensis in seasonal rainwater pools for a period of three years. Snail populations were progressively reduced to approximately 1% of the numbers in untreated pools. There was little or no evidence of acquisition of new infection by children in the area during the period of intervention. The intensity of infection in a cohort of children initially under 10 years old followed for three years fell by more than 50%, while there was a ten-fold increase in a similar group in a nearby untreated area. The mean annual cost 1982 of control per head of the population protected was £0·50 (US$0·89).

After an interval of four years the same observers re-examined six rain-forest and six savanna villages, using the same standardized techniques. The results of these surveys have previously been reported by area, i.e. rain-forest and savanna. The present paper analyses the incidence of ocular changes by village. In the rain-forest the concentrations of microfilariae in the skin were similar in the six villages and there was, in general, little difference in the incidence and/or deterioration of ocular lesions between these villages. In the savanna the corresponding quantities were much higher in the three more heavily infected villages compared with the three less heavily infected ones. The implications of these findings for the control of blindness due to onchocerciasis in the savanna are discussed.

The results of an onchocerciasis survey of total populations aged 5 years and over in 22 village groups in Cameroon rain-forest and savanna are reported. Using standardized techniques the same observers examined skin and eye lesions in 2,678 persons infected with O. volvulus , and compared them with lesions in 1,156 persons in whom the parasite was not detected.

The intensity and prevalence of proteinuria and haematuria were studied with urinanalysis reagent strips in a Gambian community in which the intensity of infection with Schistosoma haematobium was high. The level of proteinuria present was shown to be related to the intensity of infection. Follow-up for 12 months showed that infected subjects with heavy proteinuria had a good prognosis. These findings suggest that the urinary protein in such subjects is likely to originate from lesions in the bladder and ureters and that advanced glomerular pathology is probably rare. The relationship of the levels of proteinuria and haematuria to the egg count suggests they may be parameters which could have value as indications for chemotherapy. Detailed study showed that the effect of treating all the subjects who had both 30 mg/100 ml or more of protein and at least a trace of haematuria would have been very similar to treating all those with an egg count of 200 ova/10 ml or more. Since urinanalysis with reagent strips is very simple and rapid it could have a role in mass chemotherapy campaigns, particularly those aimed at the identification and treatment of heavily infected subjects.