Characterisation of the T-cell response to Ebola virus glycoprotein amongst survivors of the 2013-16 West Africa epidemic.

Zaire ebolavirus (EBOV) is a highly pathogenic filovirus which can result in Ebola virus disease (EVD); a serious medical condition that presents as flu like symptoms but then often leads to more serious or fatal outcomes. The 2013-16 West Africa epidemic saw an unparalleled number of cases. Here we show characterisation and identification of T cell epitopes in surviving patients from Guinea to the EBOV glycoprotein. We perform interferon gamma (IFNγ) ELISpot using a glycoprotein peptide library to identify T cell epitopes and determine the CD4+ or CD8+ T cell component response. Additionally, we generate data on the T cell phenotype and measure polyfunctional cytokine secretion by these antigen specific cells. We show candidate peptides able to elicit a T cell response in EBOV survivors and provide inferred human leukocyte antigen (HLA) allele restriction. This data informs on the long-term T cell response to Ebola virus disease and highlights potentially important immunodominant peptides.

Predictors of immunity after a major serogroup W-135 meningococcal disease epidemic, Burkina Faso, 2002.

BACKGROUND: The African meningitis belt undergoes recurrent epidemics caused by Neisseria meningitidis serogroup A. During 2002, Burkina Faso documented the first large serogroup W-135 (NmW-135) meningococcal disease epidemic. To understand the emergence of NmW-135, we investigated meningococcal carriage and immunity. METHODS: Immediately after Burkina Faso's epidemic, we conducted a cross-sectional survey of meningococcal carriage and seroprevalence in an epidemic and a nonepidemic district. We identified predictors of elevated NmW-135 serum bactericidal activity (SBA), a functional correlate of protection, using multivariate logistic regression. RESULTS: The NmW-135 carriage rate was 25.2% in the epidemic district and 3.4% in the nonepidemic district (P<.0001). Compared with residents of the nonepidemic district, those of the epidemic district had higher geometric mean titers of NmW-135 SBA (P<.0001). NmW-135 SBA titers>or=1:8, an estimated protective threshold, were observed in 60.4% and 34.0% of residents of the epidemic and nonepidemic district, respectively (P=.0002). In a multivariate model, current NmW-135 carriage, age, and residence in the epidemic district were independent predictors of having an NmW-135 SBA titer>or=1:8. CONCLUSIONS: Extensive NmW-135 carriage and transmission in the epidemic area caused residents to acquire natural immunity. Serial carriage and seroprevalence surveys could establish the duration of immunity in the population. The persistent circulation of NmW-135 underscores the potential for periodic NmW-135 epidemics in Africa.

Migration as a risk factor for measles after a mass vaccination campaign, Burkina Faso, 2002.

BACKGROUND: Shortly after a measles supplementary immunization activity (SIA) targeting children from 9 months to 14 years of age that achieved high coverage, Burkina Faso had a large, serologically confirmed measles outbreak. To investigate the causes of this first reported failure of a widely successful measles control strategy we conducted a case-control study. METHODS: Serologically confirmed measles cases aged > or =9 months at the time of the SIA in 6 heavily affected districts were frequency matched on age to 3 controls recruited from people frequenting health centres in the same districts. RESULTS: Between January and July 2002, 1287 measles cases were reported throughout Burkina Faso. Of the 707 cases that were serologically confirmed, 358 (51%) were from 9 months to 14 years of age and 265 (37%) were > or =15 years of age. Among cases and controls from 9 months to 14 years of age significant risk factors for measles were lack of measles vaccination and, in the unvaccinated, recent travel to Cote d'Ivoire. Of the recent measles cases in Cote d'Ivoire 54% were there when exposed to measles. Among adults, risk factors included non-vaccination and the lack of school attendance during childhood. Vaccine effectiveness was estimated to be 98%. CONCLUSIONS: Migration of children between Cote d'Ivoire and Burkina Faso played a major role in the failure of the SIA to interrupt measles transmission. Synchronization of measles control activities should be a high priority in countries with regions where much migration occurs.

Measles incidence before and after mass vaccination campaigns in Burkina Faso.

Burkina Faso conducted mass measles vaccination campaigns among children aged 9 months to 4 years during December 1998 and December 1999. The 1998 campaign was limited to six cities and towns, while the 1999 campaign was nationwide. The last year of explosive measles activity in Burkina Faso was 1996. Measles surveillance data suggest that the 1998 urban campaigns did not significantly impact measles incidence. After the 1999 national campaign, the total case count decreased during 2000 and 2001. However, 68% of measles cases occurred among children aged 5 years or older who were not included in the mass vaccination strategy. During 2000 and 2001, areas with high measles incidence were characterized by low population density and presence of mobile and poor populations. Measles control strategies in Sahelian Africa must balance incomplete impact on virus circulation with cost of more aggressive strategies that include older age groups.

Long-term disease surveillance in Bandundu region, Democratic Republic of the Congo: a model for early detection and prevention of Ebola hemorrhagic fever.

After the large-scale outbreak of Ebola hemorrhagic fever (EHF) in Bandundu region, Democratic Republic of the Congo, a program was developed to help detect and prevent future outbreaks of EHF in the region. The long-term surveillance and prevention strategy is based on early recognition by physicians, immediate initiation of enhanced barrier-nursing practices, and the use of an immunohistochemical diagnostic test performed on formalin-fixed skin specimens of patients who die of suspected viral hemorrhagic fever. The program was implemented in September 1995 during a 4-day workshop with 28 local physicians representing 17 of 22 health zones in the region. Specimen collection kits were distributed to clinics in participating health zones, and a follow-up evaluation was conducted after 6 months. The use of a formalin-fixed skin specimen for laboratory confirmation of EHF can provide an appropriate method for EHF surveillance when linked with physician training, use of viral hemorrhagic fever isolation precautions, and follow-up investigation.

Meningitis outbreaks and vaccination strategy.

Three outbreaks of meningitis caused by Neisseria meningitidis serogroup A (subgroup III) are described: Niger (1991), Burundi (1992), and Guinea (1993). These outbreaks showed unusual characteristics: a shorter inter-epidemic interval (Niger), unusual geographical location outside the meningitis belt (Burundi and Guinea), and high age-specific attack rates in all age groups (Burundi and Guinea). Mass immunization campaigns mobilized considerable human and financial means (US $322,000 and 3000 person-days of work for health personnel to immunize 629,000 people in Guinea). The vaccination coverage was over 80% in densely populated areas (Burundi and urban Guinea), but below 50% in less populated areas (24/27 and 26/30 sub-districts in Niger and Guinea, respectively). The preventive fraction (proportion of cases prevented by vaccination) was substantial in Guinea (35% for a vaccine efficacy of 85%) and was higher where the campaign was initiated earlier. An 'alert' threshold indicating the onset of an epidemic of 15/100,000 cases in one week showed good sensitivity (94%), specificity (98%) and positive predictive value (89%) in Burundi, permitting quick decision making outside the meningitis belt. These 3 meningococcal meningitis outbreaks show the need for epidemic emergency preparedness and for vigilance on the whole African continent.

Goitrous endemic in Guinea.

We identified a major goitrous area in the Republic of Guinea, characterised by an overall goitre prevalence of 70% in adults. Thyroid swelling was sometimes present at birth and affected 55% of schoolchildren. A difference between sexes appeared at puberty. Endemic cretinism, mainly in its myxoedematous form, was found in about 2% of goitrous patients. In this region, iodine deficiency is the primary causative factor (median urinary concentrations of 16 micrograms/L, and in 69% of inhabitants below the critical threshold of 20 micrograms/L). The diet contained substantial amounts of thiocyanate anions (median 6 mg/L in urine and in 27%, more than 10 mg/L) likely to further depress iodine bioavailability. Other dietary compounds, notably flavonoids were suspected to contribute. Overall nutritional and general health appeared satisfactory. The affected population is borderline euthyroid with a trend towards hypothyroidism in protracted disease. This area of Guinea may be regarded as the epicentre of the west African endemic and as one of the most severely goitrous regions ever described, requiring urgent public health measures.

Intra-household correlations in maternal-child nutritional status in rural Guinea: implications for programme-screening strategies.

It is commonly assumed in public health practice that households in developing country settings are relatively homogeneous with respect to nutritional status. To the extent that this assumption is valid, nutritional assessments of mothers or individual children would provide an effective screening mechanism for household-level maternal-child nutritional risk. However, there has been no confirmation of the strength of intra-household correlations in nutritional status among women and children. Using data from a cross-sectional survey undertaken in 1990 in rural central Guinea, the present study investigates the nature of within-household relationships in maternal and child nutritional status and considers the implications for programme screening strategies. Mothers and their surviving children under 5 years of age are the focus of the analysis. Correlations between maternal and child nutritional levels are assessed and the performance of maternal-child nutritional indicators as screening tools for household nutritional risk are formally evaluated by analysing the sensitivity, specificity, and positive-negative predictive values of various indicators.

PIP: The authors explore to what extent households may be identified as being at risk of maternal-childhood malnutrition on the basis of a nutritional assessment of one household member. Cross-sectional survey data collected in 1990 from the central Guinean provinces of Labe, Tougue, Lelouma, Dolaba, and Pita, on 780 mothers and their 1118 surviving children under 5 years of age are the focus of the analysis. The survey had been conducted to obtain baseline data on nutrition and health problems in the region. Investigators assessed correlations between maternal and child nutrition, and formally evaluated the performance of maternal-child nutritional indicators as screening tools for household nutrition risk. Although significant intra-households correlations were found with regard to nutritional status among women and children, the data clearly indicate the inefficiency of screening for household-level maternal-child nutritional risk on the basis of anthropometric indicators for mothers and/or individual children under age five years.

Use of a rapid test and an ELISA for HIV antibody screening of pooled serum samples in Lubumbashi, Zaire.

Pools with a size of 3 and 5 were prepared by mixing one HIV confirmed HIV-1 seropositive serum with either 2 or 4 HIV seronegative sera at the Regional HIV Laboratory in Lubumbashi, Zaire. These pools were assessed in a blind fashion by ELISA (Vironostika anti-HTLV-III microELISA system, Organon Technika). Similarly constituted pools of 3 samples were assayed by a rapid test with visual reading (HIVCHEK 1 + 2, Dupont de Nemours). With the HIVCHEK, pooling was achieved on the test device itself by dropping consecutively 3 different serum samples on the devices's membrane. After the last serum was soaked in, wash fluid and conjugate were added. Results of the pooling experiments were compared with testing sera individually. The ELISA results from pools and from individual tested samples matched completely if, and only if, the final dilution of individual samples in the reagent medium was the same as recommended by the manufacturer for testing of individual samples. With the HIVCHEK a sensitivity of 99-100% was obtained with pooled sera. Both approaches seemed sensitive enough to enable their use for screening of blood donors and patient management, but a prospective study to validate these preliminary results is necessary.

Prevention of blood-borne HIV transmission using a decentralized approach in Shaba, Zaire.

OBJECTIVE: To prevent blood transfusion-acquired HIV infection with a decentralized approach to HIV screening of blood donors, using an instrument-free rapid test. SETTING: Shaba province, Zaire (496,877 km2). METHODS: The programme consisted of training health-care workers, distribution of a rapid HIV-antibody test (DuPont's HIVCHEK) for screening of all blood donations, and quality control of testing by a regional reference centre. RESULTS: Over a 2-year period, 11,940 rapid tests were distributed to 37 hospitals, covering 75% of all hospital beds outside the copper mine's health system in Shaba. Eighty-five per cent of the tests were used to screen blood donors (5.4% positive test rate) and 13% to test patients (39.7% positive test rate). At least 265 cases of HIV-positive blood donation were prevented, at an estimated cost of 137-279 ECU per case. Only 26% of initially positive specimens reached the central laboratory for supplemental testing, and sterile transfusion equipment and blood-grouping reagents were frequently unavailable. The lack of transport and communications and a deteriorating health system were major constraints. CONCLUSIONS: District hospitals in Africa are often long distances from major cities, difficult to reach for most of the year, and perform a small number of transfusions. In this context a classical centralized regional blood bank may not be a feasible option to ensure safe blood transfusions. However, safe blood transfusion can be achieved with a decentralized approach using a rapid test, provided that minimum standards of health-care services are available.

PIP: This program aimed at preventing blood transfusion-acquired HIV infection with a decentralized approach to HIV screening of blood donors using an instrument free raid test was initiated in Shaba province in Zaire (496,877 sq. km and included training of health care workers, distribution of a rapid HIV-antibody test (DuPont's HIVCHEK) for screening of all blood donations, and quality control of testing by a regional reference center. Over a 2-year period, 11,940 rapid tests were distributed to 37 hospitals, covering 75% of all hospital beds outside the copper mine's health system in Shaba. 85% of the tests were used to screen blood donors (5.4% positive test rate) and 13% to test patients (39.7% positive test rate). At least 265 cases of HIV-positive blood donation were prevented at an estimated cost of 137-279 ECU per case. Only 26% of initially positive specimens reached the central laboratory for supplemental testing, and sterile transfusion equipment and blood-grouping reagents were frequently unavailable. The lack of transport and communications and a deteriorating health system were major constraints. District hospitals in Africa are often long distances from major cities, difficult to reach for most of the year, and perform a small number of transfusions. In this context, a classical centralized regional blood bank may not be a feasible option to ensure safe blood transfusions. However, safe blood transfusion can be achieved with a decentralized approach using a rapid test, provided that minimum standards of health care services, are available.

[Vaccination against measles at 6 months of age]. / Etude de la vaccination contre la rougeole a six mois.

Measles immunization with the Edmonston Zagreb stain was carried out in 71 six-month-old infants. Proportions of subjects with immunity were 91% among the 47 subjects retested before one year of age and 100% among the 28 subjects retested between two and three years of age. These results support the WHO recommendation that measles immunization should be given at the age of six months. The concerns expressed by some about possible adverse effects of early measles immunization (decreased immune defenses) are discussed, as well as the transfer of maternal antibodies and persistence of these antibodies in the child. The obstacles to such studies in developing countries, including the need for repeated phlebotomies with centrifugation of specimens and freezing of sera, could be circumvented by the use of filter paper dried blood spot samples which seem to provide reliable results although with values somewhat lower than those found in frozen sera.

A simplified and less expensive strategy for confirming anti HIV-1 screening results in a diagnostic laboratory in Lubumbashi, Zaire.

The conventional algorithm for HIV testing based on the confirmation of all positive anti-HIV screening reactions by Western blot (WB) is too expensive for developing countries. We investigated the validity of confirming positive screening assay reactions by a second screening test, limiting the use of the supplemental assay to the discrepant test results (algorithm 3), or screening all sera with 2 different assays and retesting all discrepant results by a supplemental assay (algorithm 4) on a panel of 519 sera in a regional reference laboratory in Lubumbashi, Zaire. Combining the Vironostika anti-HTLV-III ELISA with HIV Chek 1 + 2 or Clonatec Rapid HIV 1/2 Ab on all samples and retesting the discrepant results in WB or a line immunoassay (INNO-LIA) (algorithm 4), yielded a sensitivity of 100% and specificities of 98.4% and 99.0% respectively, at costs of 7.3 US $ and 9.3 US $ per test, respectively, for a 40% prevalence of HIV antibody positive samples. The conventional algorithm scored a sensitivity of 97.1% and a specificity of 100% for 11.3 US $ per test. The testing strategy of combining HIV Chek 1 + 2 and Clonatec Rapid HIV 1/2 Ab, an interesting option for small isolated centra, had a 96.6% sensitivity, but yielded only a slightly better specificity of 99.0%, as compared to 97.8% for HIV Chek alone. The price of combining the two simple assays using algorithm 3 was 6.8 US $ per test, using algorithm 4 was 10.6 US $. HIV testing strategies based on ELISA and a simple HIV test are a valuable alternative for reference laboratories faced with a high prevalence of HIV positive samples.