Morphological and genetic variability within Aedes aegypti in Niakhar,Senegal

Aedes aegypti (Linné, 1762) is a major vector of arboviruses such as Yellow Fever, Dengue and Chikungunya. In Africa, where the species exhibits major variations in morphology, ecology, behavior and vector competence, two subspecies have been described: a light form, named Ae. aegypti aegypti (Aaa) with highly domestic and anthropophilic habits and a cosmotropical distribution; and a dark form, referred to as Ae. aegypti formosus (Aaf), which is endemic to Africa and thrives in sylvan environments. In East Africa, both forms were described to occur in sympatry whereas only Aaf was reported from Central/West Africa. However, recent findings suggest Aaa was also common in Senegal. Here, we report on a longitudinal survey of morphological and genetic variability of Ae. aegypti sampled in the rural environment of Niakhar, Senegal. In agreement with recent findings, most of specimens we analyzed were classified as Aaa suggesting typical Aaf was scarce in the studied area. Among Aaa, significant temporal variations in abdominal pale scales pattern were detected. Depending on the season and the nature of larval breeding places, the specimens (particularly females) tend to segregate in two main morphological groups. Microsatellite-based estimates of genetic differentiation did not provide any clear evidence that the two groups were genetically distinct. Overall, these results improve our understanding of the diversity of Ae. aegypti in West Africa, where data are crucially lacking.     

Epidemic measles in an isolated unvaccinated population, India

Between June and September, 1986, an outbreak of measles occurred in Pilkhi Primary Health Centre area (population 56,000) in Tehri Garhwal district, Uttar Pradesh, India. Overall, 1092 cases were identified and 62 died; case-fatality ratio was 5.7%. Illness was restricted primarily to children below 15 years of age; 38% cases were in children under 5 and 58% between 5-14 years of age. To better characterize the outbreak, a survey was conducted in 13 affected villages. The age of the cases ranged from 5 months to 19 years (median = 7.0 years). The age-specific attack rates were 22.4%, 54.5%, 46.2% and 35.3% for children under 1, 1-4, 5-9, 10-14 years of age respectively. In as many as four villages, the attack rate in children below ten was 80% or more. Secondary attack rate among family members was 70%. Overall, 82% of children with measles developed complications which consisted mainly of pneumonia, diarrhoea and dysentery. The age-specific case-fatality ratios in infants and children 1-4 years of age were 23.1% and 11.5% respectively; thereafter the rates tended to decline with increasing age and was higher in females than in males (less than 0.05). Pneumonia which was a complication in 39% of measles cases contributed to 56% of deaths. Traditional beliefs and customs in the area were strong and did not encourage treatment of measles cases. Although a measles vaccination programme has been launched in India since 1985, only 30 districts could be covered during the first year and another 90 during 1986.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distributions of mortality risk attributable to low nutritional status in Niakhar, Senegal

This study proposes a method for computing the distributions of mortality risk attributable to malnutrition among children of developing countries. Population distributions of nutritional status were adjusted with a normal curve and the relation between mortality and nutritional status was fitted with a linear logistic model after controlling for age. The attributable risk for mortality could therefore be computed at any threshold of low nutritional status. The method was applied in Niakhar, Senegal, where a comprehensive study of the relation between nutritional status and mortality was conducted in 1983-1984 on approximately 5,000 children, 6-59 mo of age. The anthropometric indicators used were Z-scores of weight-for-age, weight-for-height, height-for-age, head circumference-for-age, arm circumference-for-age, triceps skinfold-for-age, and subscapular skinfold-for-age, plus arm circumference, body mass index, and 2 composite indicators. Population attributable fraction varied according to indicators selected and ranged from 31% (head circumference) to 65% (arm circumference). The 2 composite indicators summarizing the whole nutritional status provided the same value for the population attributable fraction (59 and 60%, respectively). Classic thresholds of mild, moderate, and severe malnutrition are presented, as well as the bivariate distribution of wasting and stunting. Whatever the indicator used, mortality attributable risks appeared evenly distributed along the scale of low nutritional status. Our findings question the value of using classic thresholds of mild, moderate, and severe malnutrition (developed by clinicians for practical purposes) for nutritional epidemiology.     

Immune response to measles vaccine in 6-month-old infants of measles seronegative mothers

Determinants of measles vaccine-induced immune response in infancy include maternal immune status and the infant's age at immunization. In a previously published study, 74% of 19 6-month-old infants developed neutralizing antibody. Two of the infants were born to measles seronegative mothers¹. In order to (1) assess the prevalence of measles seronegativity in a population of US mothers born after 1960 and (2) assess the immunogenicity of standard titer measles vaccine in 6-month-old infants of measles seronegative mothers, mothers with healthy term (≥37 weeks gestation) infants attending well child care clinics at MetroHealth Medical Center were prospectively screened for measles antibody by EIA. If negative, maternal samples were retested for neutralization (NT) antibody. Fifteen of 169 women were seronegative by both assays. Six-month-old infants of 9 of these 15 seronegative mothers were enrolled in the pediatric vaccine study. Serological response of these 9 infants to monovalent measles vaccine (Attenuvax^®) was compared to the responses of 17 6-month-old infants of seropositive mothers and 15 15-month-old toddlers from our previous study. All 9 infants of seronegative mothers became EIA seropositive after the vaccine compared to 9 of 17 6-month-old infants born to seropositive mothers (p = 0.02). Differences in NT seroconversion rates (100% vs 70.6%) were not statistically significant. The comparison group of 15-month-old vaccinees showed 100% seroconversion by both assays. The NT geometric mean titer (GMT) was higher in the 15-month-old toddlers than in the 6-month-old infants born to seronegative mothers (87.2 vs 33.9, p < 0.01), suggesting age-related differences in humoral immune response unrelated to passively transferred maternal antibody.     

Climate variability and number of deaths attributable to malaria in the Niakhar area, Senegal, from 1984 to 1996

There are a number of reasons why climate, in certain physical and social environments, could have an impact on the epidemiology of malaria. Events, such as floods or drought, are related to the number of malaria cases and deaths, both seasonally and interannually. At a smaller scale, this study analyses the relation between climate variability and the variability in the number of deaths attributable to malaria in Niakhar, Senegal. The Niakhar area has a population of 30,000 and has been under demographic surveillance system since 1984. The rainfall in this region is highly seasonal, with a rainfall maximum in August and almost no rain between October/November and May/June. In addition to this seasonal cycle, rainfall also varies greatly from year to year (interannual variation). Over the 13 years, there were 661 deaths attributed to malaria with a marked interannual variability (range from 23 to 100, with a median of 43). There was also a strong seasonality in mortality, with nearly all deaths (89.1%) occurring between August and December. The number of deaths peaks in October, two months after the rainfall peak. Standardised monthly values were calculated for each climatic series (rainfall, relative humidity, temperature) as well as standardised five-month and monthly values of the number of deaths attributed to malaria between August and December. Correlation coefficients were calculated between these standardised values. The correlation between the variability in August rainfall and the variability in the number of deaths attributed to malaria between August and December was positive and statistically significant (r = +0.61, p = 0.02). In addition, highly significant cross-correlations were found between monthly rainfall series and monthly mortality series at one- and two-month lag (r = + 0.43, p = 0.0004 for one-month lag; r = + 0.26, p = 0.03 for two-month lag). This correlation is somewhat lower than the correlation of August rainfall alone with August to December mortality, but the result adds confidence to the signal given the increased degrees of freedom in the analysis. Similar, but slightly weaker, results were found when precipitation data were replaced with surface humidity data. Results with temperature were less clear; while temperature could in some circumstances have a direct impact on malaria, in this case here it is possible that the weak negative correlation between malaria deaths and temperature arises mainly because precipitation is physically connected to both the indices, correlating positively with malaria and negatively with temperature. The availability of a continuous demographic and medical survey since 1984 in a region of highly variable rainfall has created a rare opportunity to analyse with some confidence a climate versus malaria relationship. The findings are consistent with our understanding of the proposed link between rainfall and conditions for the reproduction of the malaria vector, leading to a lag time (here of one to two months) between anomalies of rainfall and deaths attributable to malaria. These results may have practical implications in Sub-Saharan regions marked by a great seasonal and interannual variability in rainfall by providing a simple tool to forecast the impact of climate variability on malaria mortality.     

Childhood mortality and probable causes of death using verbal autopsy in Niakhar, Senegal, 1989-2000

BACKGROUND: In African rural settings, medically certified information on causes of death is largely lacking. The authors applied the verbal autopsy to identify causes of death before 15 years old in a rural area of Senegal where a demographic surveillance system is operating. METHODS: Between 1989 and 2000, a postmortem interview was conducted using a standardized questionnaire which was independently reviewed by two physicians who assigned the probable underlying cause of death. Discordant diagnoses were discussed by a panel of physicians. Causes of death were grouped into a few categories; cause-specific mortality rates and fractions were generated. RESULTS: Between 1989 and 1997, all-cause mortality fluctuated. Diarrhoeal diseases, malaria and acute respiratory infections explained between 30% and 70% of the mortality before 10 years of age. In children 1-9 years old, malaria death rate increased between 1989 and 1994 and thereafter did not change. The 1998-2000 years were marked by a peak in mortality, attributed to a meningitis outbreak in children more than one year old paralleled by an increase in death rate from fever of unknown origin, diarrhoeal diseases, and acute respiratory infections in children under 5 years. CONCLUSIONS: Verbal autopsy provided useful information on the mortality structure responsible for the 1998-2000 peak in mortality. It underlined that, outside outbreak situations, malaria was a leading cause of death for 1-9 year old children and that diarrhoea, acute respiratory infections, or fever from unknown origin accounted for up to 50% of the deaths among the children under 5 years.     

浙江省一起由免疫接种空白导致的流动人口麻疹暴发

目的 为核实浙江省某村1名麻疹确诊患儿家长报告同村有多名发热、出疹病例,并调查暴发原因.方法 疑似病例定义为2010年6月1日至8月3日,该村及其所在街道和周围邻村居民中出现发热伴出疹症状者;确诊病例为疑似病例中血清麻疹IgM抗体阳性者.在全村范围开展逐户搜索,通过中国疾病预防控制信息系统搜索该村所在街道及相邻村的麻疹报告病例.对全村8月龄至14岁流动儿童开展回顾性队列研究.结果 该村共发现19例麻疹病例(17例确诊和2例疑似),均为流动人口,罹患率以1～2岁组为最高(13%).首发病例6月4日抵该村后发病,在非法私人诊所就医,但未向卫生部门报告疫情,卫生部门通过患儿家长报告识别暴发时,疫情已持续1个月.315名8月龄至14岁流动儿童中,麻疹疫苗接种率为81%.无麻疹疫苗接种史的61名流动儿童中,16名有明确病例接触史者发病风险(88%,14/16)高于45名无病例接触史者(4.4%,2/45)(Fisher精确概率法,RR=20,95%CI:5.7～94).结论 该村流动儿童麻疹疫苗接种率低,非法私人诊所不按规定对病例进行报告、隔离和医疗诊治,是导致此次疫情暴发的主要原因.     

An evaluation of measles, mumps and rubella vaccine in a population of Yorkshire infants

In October 1988 combined measles, mumps and rubella (MMR) vaccination replaced monocomponent measles as part of the routine childhood vaccination programme in the United Kingdom. Prior to this policy change a study was undertaken in 335 children aged 15 months, to evaluate the clinical reactions and immunogenicity of the new combined MMR vaccine (Trimovax, Immravax, Merieux), in comparison with an established monocomponent measles vaccine (Rouvax, Merieux). Parents were asked to select whether their child should receive MMR vaccine or measles monocomponent; over 95% chose MMR. Children who were given the MMR vaccine had seroconversion rates of 96% for measles, 97% for mumps and 100% for rubella, whilst those who received monocomponent measles vaccine had a seroconversion rate of 100%. The number of side effects reported was similar with both vaccines; all were mild and self-limiting. The results from this study confirm the efficacy and low reactogenicity of MMR vaccine and support its use as part of the routine childhood immunisation programme in the United Kingdom.     

Role of schools in the transmission of measles in rural Senegal: implications for measles control in developing countries

Patterns of measles transmission at school and at home were studied in 1995 in a rural area of Senegal with a high level of vaccination coverage. Among 209 case children with a median age of 8 years, there were no deaths, although the case fatality ratio has previously been 6-7% in this area. Forty percent of the case children had been vaccinated against measles; the proportion of vaccinated children was higher among secondary cases (47%) than among index cases (33%) (prevalence ratio = 1.36, 95% confidence interval (CI) 1.04-1.76). Vaccinated index cases may have been less infectious than unvaccinated index cases, since they produced fewer clinical cases among exposed children (relative risk = 0.55, 95% CI 0.29-1.04). The secondary attack rate was lower in the schools than in the homes (relative risk = 0.31, 95% CI 0.20-0.49). The school outbreaks were protracted, with 4-5 generations of cases being seen in the two larger schools. Vaccine efficacy was found to be 57% (95% CI -23 to 85) in the schools and 74% (95% CI 62-82) in the residential compounds. Measles infection resulted in a mean of 3.8 days of absenteeism per case, though this did not appear to have an impact on the children's grades. Among the index cases, 56% of children were probably infected by neighbors in the community, and 7% were probably infected at health centers, 13% outside the community, and 24% in one of the three schools which had outbreaks during the epidemic. However, most of the school-related cases occurred at the beginning and therefore contributed to the general propagation of the epidemic. To prevent school outbreaks, it may be necessary to require vaccination prior to school entry and to revaccinate children in individual schools upon detection of cases of measles. Multidose measles vaccination schedules will be necessary to control measles in developing countries.     

The sequence of vaccinations and increased female mortality after high-titre measles vaccine: trials from rural Sudan and Kinshasa

OBJECTIVE: West African studies have hypothesized that increased female mortality after high-titre measles vaccine (HTMV) was due to subsequent diphtheria-tetanus-pertussis (DTP) and inactivated polio vaccine (IPV) vaccinations. We tested two deductions from this hypothesis in HTMV studies from rural Sudan and Kinshasa; first, there should be no excess female mortality for HTMV recipients when DTP was not given after HTMV and second, excess female mortality should only be found among those children who received DTP after HTMV. STUDIES: The Sudanese trial randomised 510 children to Edmonston-Zagreb (EZ) HTMV, Connaught HTMV or a control vaccine (meningococcal). Both the Connaught HTMV and the control group received standard measles vaccine at 9 months. In the Kinshasa study 1023 children received one dose of HTMV at 6 months or two doses at 312 and 912 months of age. FINDINGS: First, the Sudan trial is one of the few randomised studies of measles vaccine; the EZ HTMV group had lower mortality between 5 and 9 months of age than controls, the mortality ratio (MR) being 0.00 (p = 0.030). This effect was not due to prevention of measles infection. Second, both studies provided evidence that HTMV per se was associated with low mortality. In a combined analysis comparing both HTMV groups with controls, the HTMV groups had a MR of 0.09 (0.01-0.71) between 5 and 9 months of age. In Kinshasa, the HTMV recipients who did not receive simultaneous DTP had an annual mortality rate of only 1.0% between 6 months and 3 years of age. Third, the female-male MR was related to subsequent DTP vaccinations. In Kinshasa, the female-male MR was only 0.40 (0.13-1.27) among the HTMV recipients who did not receive further doses of DTP. In Sudan, the female-male mortality ratio in the EZ group was 3.89 (95% CI 1.02-14.83) and the female-male MR increased with number of doses of DTP likely to have been given during follow-up (trend, p = 0.043). Fourth, in Kinshasa, mortality was higher among children who had received HTMV and DTP simultaneously than among children who had received HTMV alone (MR = 5.38 (1.37-21.2)). CONCLUSIONS: Measles vaccine is associated with non-specific beneficial effects. When not given with DTP, HTMV per se was associated with low mortality. Increased female mortality was not found among children who did not receive DTP after HTMV. Hence, our deductions were supported and the sequence or combination of vaccinations may have an effect on sex-specific mortality patterns in low-income countries.     

西安市麻疹疫苗免疫接种情况的调查

目的　为了掌握西安市婴儿麻疹疫苗 (以下简称MV)基础免疫接种情况 ,以进一步提高免疫成功率。方法　在西安市城区和郊区随机抽查 5 7名 0岁组健康婴儿 ,采用酶联免疫吸附法 (ELISA)测定血清麻疹IgG抗体水平。结果　免疫前MV阳性率为 2 8 0 7% ,GMT 1∶4;免疫后MV阳性率为 98 2 5 % ,GMT 1∶1666;免疫前后阳性率、抗体平均滴度经统计分析 ,差异有非常显著性 (P <0 .0 1) ;对MV免疫后不同性别、不同地区的抗体阳性率 ,平均滴度进行统计分析 ,差异无显著性 (P >0 0 5 )。结论　婴儿在出生后 8个月 ,母体胎传抗体逐渐衰减 ,致MV阳性率极低 ,只需按现行的免疫程序及时有效地接种MV ,就能获得保护抗体 ,达到控制麻疹发病的目的。同时也说明MV的免疫成功与否不受性别和地区的影响。     

Assessing measles vaccine failure in Tianjin,China

Despite increasing global measles vaccination coverage, progress toward measles elimination has slowed in recent years. In China, children receive a measles-containing vaccine (MCV) at 8 months, 18–24 months, and some urban areas offer a third dose at age 4–6 years. However, substantial measles cases in Tianjin, China, occur among individuals who have received multiple MCV doses. This study describes the vaccination history of measles cases 8 months – 19 years old. Data came from measles cases in Tianjin’s reportable disease surveillance system (2009–2013), and from a case control study (2011–2015). Twenty-nine percent of those in the surveillance dataset and 54.4% of those in the case series received at least one dose of MCV. The minimum and median time-to-diagnosis since vaccination revealed an increase in time since vaccination for incremental doses. Considerable measles cases in Tianjin occur in vaccinated children, and further research is needed to understand the reasons for vaccine failure.     

Lack of efficacy of the standard potency Edmonston-Zagreb live, attenuated measles vaccine in African infants.

The efficacy of standard potency Edmonston-Zagreb (E-Z) measles vaccine was tested in a randomized trial of Black infants in a rural area of South Africa where a measles epidemic was occurring. The following immunization schedules were used: 48 infants aged 4-8.5 months who received 3.9 log 50 infectious units of E-Z vaccine (group A); 48 infants aged 4-8.5 months who received 3.28 log 50 infectious units of Schwarz vaccine (group B); and 28 infants aged greater than 9 months who received 3.28 log 50 infectious units of Schwarz vaccine and served as controls (group C). For infants aged less than 23 weeks who were given either the E-Z or Schwarz vaccine, the number of seropositives was low (28%), irrespective of the pre-vaccination level of measles antibody. There was a higher number of seropositives (68%) among those in the age range greater than 23 weeks to less than 36 weeks who received the E-Z vaccine rather than the Schwarz vaccine (36%). When administered to children aged greater than 36 weeks, the Schwarz vaccine produced a satisfactory, though suboptimal response rate (61%). There was no correlation between seropositivity and pre-vaccination measles antibody status. Use of the standard dose of E-Z vaccine may have been one of the factors for this poor response, and this supports the WHO recommendation that titres higher than the standard potency vaccine are needed if 6-month-old infants are to be successfully immunized against measles.