Measles vaccination and reduction in child mortality: A community study from Guinea-Bissau

doi:10.1016/S0163-4453(84)93192-X

Journal of Infection

Volume 8, Issue 1, January 1984, Pages 13-21

https://doi.org/10.1016/S0163-4453(84)93192-X Get rights and content

Summary

Earlier studies have suggested that general measles vaccination programmes should not be made a priority in developing countries because the presumably malnourished children saved from measles are likely to die from something else. Recent community studies indicate, however, that malnutrition is not the cause of high measles mortality. In an urban community in Guinea-Bissau, child mortality has been registered for a period of 3 years; 1 year before and 2 years after the introduction of a general measles vaccination program. In the years following the introduction of measles vaccination, mortality for children aged 6 to 35 months has significantly diminished. Though this is not a controlled study of vaccinated and unvaccinated children, much of the reduced mortality can apparently be attributed to the protective effect of measles vaccination. Children with a history of earlier measles infection had a significantly higher mortality rate than children vaccinated against measles. Rather than being a mechanism of natural selection taking the weakest children, measles apparently aggravates the condition of many children, leading to delayed excess mortality. In areas where the case fatality rate is high, vaccination against measles should be made an indispensable part of primary health care.

References (23)

MorleyD
Overview of the present situation as to measles in the developing world
Trans R Soc Trop Med Hyg
(1975)
HendrickseRG
Problems of future measles vaccination in developing countries
Trans R Soc Trop Med Hyg
(1975)
AabyP et al.
Measles vaccination and child mortality
Lancet
(1981)
HopkinsDR et al.
The case for global measles eradication
Lancet
(1982)
CreeseAL et al.
Cost-benefit analysis of immunization programmes in developing countries
Bull WHO
(1980)
SinhaDP
Measles and malnutrition in a West Bengal village
Trop geogr Med
(1977)
Influence of measles vaccination on survival pattern of 7-35-month-old children in Kasongo, Zaire
Lancet
(1981)
ReyM et al.
La rougeole au Sénégal après trois ans de vaccination de masse
Bull Soc Med Afr Noire Igue frse
(1971)
MorleyD
Paediatric Priorities in the Developing World
(1973)

AabyP et al.

Measles mortality, state of nutrition, and family structure

Cited by (102)

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Immune memory was for a long time thought to be an exclusive feature of the adaptive immune system. Emerging evidence has shown that the innate immune system may exhibit memory which has been termed as trained immunity or innate immune memory. Trained immunity following vaccination may produce non-specific effects leading to reduction in morbidity and mortality from heterologous pathogens. This review looked at trained immunity as a mechanism for vaccine induced non-specific effects, mechanisms underlying trained immunity and known vaccine non-specific effects. A discussion is also made on the implications these vaccine non-specific effects may have on overall risk–benefit ratio evaluation by National Medicines Regulatory Authorities (NMRAs) during licensure of new vaccines. Epigenetic remodeling and “rewiring” of cellular metabolism in the innate immune cells especially monocytes, macrophages, and Natural Killer (NK) cells have been suggested to be the mechanisms underlying trained immunity. Trained immunity in other innate cells has largely remained elusive up to date. Non-specific effects have been extensively documented with Bacille Calmette-Guerin (BCG), measles vaccine and oral polio vaccine but it remains unclear if other vaccines may exhibit similar effects. All known vaccine non-specific effects have come from observations in epidemiological studies conducted post-vaccine licensure and roll out in target populations. It remains to be seen if early identification of non-specific effects especially those with protective benefits during the clinical development of new vaccines may contribute to the overall risk–benefit ratio evaluation during licensure by NMRAs.
Do vaccines increase or decrease susceptibility to diseases other than those they protect against?
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Contrary to the long-held belief that the effects of vaccines are specific for the disease they were created; compelling evidence has demonstrated that vaccines can exert positive or deleterious non-specific effects (NSEs). In this review, we compiled research reports from the last 40 years, which were found based on the PubMed search for the epidemiological and immunological studies on the non-specific effects (NSEs) of the most common human vaccines. Analysis of information showed that live vaccines induce positive NSEs, whereas non-live vaccines induce several negative NSEs, including increased female mortality associated with enhanced susceptibility to other infectious diseases, especially in developing countries. These negative NSEs are determined by the vaccination sequence, the antigen concentration in vaccines, the type of vaccine used (live vs. non-live), and also by repeated vaccination. We do not recommend stopping using non-live vaccines, as they have demonstrated to protect against their target disease, so the suggestion is that their detrimental NSEs can be minimized simply by changing the current vaccination sequence. High IgG4 antibody levels generated in response to repeated inoculation with mRNA COVID-19 vaccines could be associated with a higher mortality rate from unrelated diseases and infections by suppressing the immune system. Since most COVID-19 vaccinated countries are reporting high percentages of excess mortality not directly attributable to deaths from such disease, the NSEs of mRNA vaccines on overall mortality should be studied in depth.
Measles vaccination and reduced child mortality: Prevention of immune amnesia or beneficial non-specific effects of measles vaccine?
2023, Journal of Infection
Measles vaccine (MV) has been observed to reduce all-cause mortality more than explained by prevention of measles infection. Recently, prevention of “measles-induced immune amnesia” (MIA) has been proposed as an explanation for this larger-than-anticipated beneficial effect of measles vaccine (MV). According to the “MIA hypothesis”, immune amnesia leads to excess non-measles morbidity and mortality, that may last up to five years after measles infection, but may be prevented by MV. However, the benefits of MV-vaccinated children could also be due to beneficial non-specific effects (NSEs) of MV, reducing the risk of non-measles infections (The “NSE hypothesis"). The epidemiological studies do provide some support for MIA, as exposure to measles infection before 6 months of age causes long-term MIA, and over 6 months of age for 2–3 months. However, in children over 6 months of age, the MIA hypothesis is contradicted by several epidemiological patterns: First, in community studies that adjusted for MV status, children surviving acute measles infection had lower mortality than uninfected controls (44%(95%CI: 0–69%)). Second, in six randomised trials and six observational studies comparing MV-vaccinated and MV-unvaccinated children, the benefit of MV changed minimally from 54%(43–63%) to 49%(37–59%) when measles cases were censored in the survival analysis, making it unlikely that prevention of measles and its long-term consequences explained much of the reduced mortality. Third, several studies conducted in measles-free contexts still showed significantly lower mortality after MV (55%(40–67%)). Fourth, administration of MV in the presence of maternal measles antibody (MatAb) is associated with much stronger beneficial effect for child survival than administration of MV in the absence of MatAb (55%(35–68%) lower mortality). The MIA hypothesis alone cannot explain the strongly beneficial effects of MV on child survival. Conversely, the hypothesis that MV has beneficial non-specific immune training effects is compatible with all available data. Consideration should be given to continuing MV even when measles has been eradicated.
Overall effect of a campaign with measles vaccine on the composite outcome mortality or hospital admission: A cluster-randomized trial among children aged 9-59 months in rural Guinea-Bissau
2023, International Journal of Infectious Diseases
Campaigns with measles vaccine (C-MV) are conducted to eradicate measles, but prior studies indicate that MV reduces non-measles mortality and hospital admissions too. We hypothesized that C-MV reduces death/hospital admission by 30%.
Between 2016-2019, we conducted a non-blinded cluster-randomized trial randomizing village clusters in rural Guinea-Bissau to a C-MV targeting children aged 9-59 months. In Cox proportional hazards models, we assessed the effect of C-MV, obtaining hazard ratios (HR) for the composite outcome (death/hospital admission). We also examined potential effect modifiers.
Among 18,411 children (9636 in 111 intervention clusters/8775 in 110 control clusters), 379 events occurred (208 intervention/171 control) during a median follow-up period of 22 months. C-MV did not reduce the composite outcome (HR 1.12, 95% confidence interval 0.88-1.41). Mortality among enrolled children (5.3 intervention and 4.6 control, per 1000 person-years) was approximately half the pre-trial mortality rate (11.1 intervention and 8.9 control, per 1000 person-years). Neither planned nor explorative analyses of potential effect modifiers explained the contrasting results to prior studies.
C-MV did not reduce overall mortality or hospital admission. This might be explained by changes in disease patterns, baseline differences in health status, and/or modifying effects of other campaigns during follow-up.
Effect of early two-dose measles vaccination on childhood mortality and modification by maternal measles antibody in Guinea-Bissau, West Africa: A single-centre open-label randomised controlled trial
2022, eClinicalMedicine
Citation Excerpt :
Further research should explore whether it would be beneficial to provide MV to women of fertile age to enhance antibody transfer to their children. When measles vaccine (MV) was introduced in low-income countries a major decline in mortality occurred.1-3 The reduction was larger than explained by protection against measles; this led to the hypothesis that MV had beneficial non-specific effects (NSEs).4
Early 2-dose measles vaccine (MV) at 4 and 9 months of age vs. the WHO strategy of MV at 9 months of age reduced all-cause child mortality in a previous trial. We aimed to test two hypotheses: 1) a 2-dose strategy reduces child mortality between 4 and 60 months of age by 30%; 2) receiving early MV at 4 months in the presence versus absence of maternal measles antibodies (MatAb) reduces child mortality by 35%.
Single-centre open-label community-based randomised controlled trial in Guinea-Bissau, with 2:1 block-randomisation by sex to a 2-dose (4 + 9 months) vs. 1-dose (9 months) MV strategy. Healthy children were eligible 4 weeks after the 3rd diphtheria-tetanus-pertussis-containing vaccine. Before randomisation a blood sample was collected to determine MatAb level. The primary outcome was all-cause mortality. Hazard ratios (HR) were derived from Cox regression in the per protocol population. We tested for interactions with national campaigns with oral polio vaccine (C-OPV). Trial registration: NCT01486355.
Between August 2011-April 17th 2015, 6,636 children were enroled, 6,598[n_2-dose=4,397; n_1-dose=2,201] were included in the analysis of the primary outcome, The HR(2-dose/1-dose) between 4 and 60 months was 1.38 (95%CI: 0.92–2.06) [deaths: n_2-dose=90; n_1-dose=33]. Before the 9-month MV and the HR(1-dose/no dose) was 0.94 (0.45–1.96) [deaths: n_2-dose=21; n_1-dose=11]. The HR(2-dose/1-dose) was 0.81 (0.29–2.22) for children, who received no C-OPV [deaths/children: n_2-dose=10/2,801; n_1-dose=6/1,365], and 4.73 (1.44–15.6) for children, who received C-OPV before and after enrolment (p for interaction=0.027) [deaths/children: n_2-dose=27/1,602; n_1-dose=3/837]. In the 2-dose group receiving early MV at 4 months, mortality was 50% (20–68%) lower for those vaccinated in the presence of MatAb vs. the absence of MatAb [deaths/children: n_MatAb=51/3,132; n_noMatAb=31/1,028].
The main result contrasts with previous findings but may, though based on a small number of events, be explained by frequent OPV campaigns that reduced the mortality rate, but apparently interacted negatively with early MV. The beneficial non-specific effects of MV in the presence of MatAb should be investigated further.
ERC, Danish National Research Foundation, the Danish Council for Development Research, Ministry of Foreign Affairs, Novo Nordisk Foundation, European Union and the Lundbeck Foundation.
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Bacillus Calmette–Guérin (BCG) vaccine is currently used to prevent tuberculosis infection. The vaccine was found to enhance resistance to certain types of infection including positive sense RNA viruses. The current COVID-19 pandemic is caused by positive sense RNA, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A higher mortality rate of COVID-19 patients was reported in countries where BCG vaccination is not routinely administered, when compared to the vaccinated ones. We hypothesized that BCG vaccine may control SARS-CoV2 infection via modulating the monocyte immune response. We analyzed GSE104149 dataset to investigate whether human monocytes of BCG-vaccinated individuals acquire resistance to SARS-CoV-2 infection. Differentially expressed genes obtained from the dataset were used to determine enriched pathways, biological processes, and molecular functions for monocytes post BCG vaccination. Our data show that BCG vaccine promotes a more effective immune response of monocytes against SARS-CoV2, but probably not sufficient to prevent the infection.

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Original articleMeasles vaccination and reduction in child mortality: A community study from Guinea-Bissau

Summary

Trans R Soc Trop Med Hyg

Trans R Soc Trop Med Hyg

Lancet

Lancet

Cost-benefit analysis of immunization programmes in developing countries

Bull WHO

Measles and malnutrition in a West Bengal village

Trop geogr Med

Influence of measles vaccination on survival pattern of 7-35-month-old children in Kasongo, Zaire

Lancet

La rougeole au Sénégal après trois ans de vaccination de masse

Bull Soc Med Afr Noire Igue frse

Paediatric Priorities in the Developing World

Measles mortality, state of nutrition, and family structure

Original article
Measles vaccination and reduction in child mortality: A community study from Guinea-Bissau