BRAZIL: Microcephaly & Zika Virus/Vírus de microcefalia & Zika/Microcefalia y Zika Virus (Initiated on 12/25/2015 - Merry Christmas)

This article presents interesting observations/suggestions to combat increasing microcephaly cases in new borns

(Portuguese) Este artigo apresenta observações interessantes / sugestões para combater o aumento de casos microcefalia em recém-nascidos

(Spanish) Este artículo presenta interesantes observaciones y / o sugerencias para combatir el aumento de casos de microcefalia en los recién nacidos

WHY MICROCEPHALY?

The following set of articles caught our attention:







English -> This article is for Epidemiologists, GIS specialists, Medical practitioners, Public Health specialists, Journalists, Vaccination experts, Virologists, Economists  & most importantly, mothers of the world.

Traduz Google Português -> Este artigo é para epidemiologistas, especialistas em GIS, os médicos, especialistas em saúde pública, jornalistas, especialistas em vacinação, virologistas, os economistas e, mais importante, as mães do mundo.

Traductor Google español -> Este artículo es para epidemiólogos, especialistas en SIG, profesionales médicos, especialistas en salud pública, periodistas, expertos de vacunación, virólogos, economistas y lo más importante, las madres del mundo.



Due to the nature of the issue being of great global concern, our PI looked into the available data, and observed some key points:

Principal Investigator(PI)'s couple of interesting prior work

1. Dengue Hemorrhagic Fever 

PI promoted awareness on Dengue & DHF through extensive literature research, and by sharing personal experience


2. MERS 

PI (for the first time ever in the history of MERS) was able to connect prior knowledge on mosquito-borne diseases to MERS; This observation, http://www.bbc.com/news/world-asia-33684981, might be a mere coincidence, but the MERS outbreak was controlled within 21 days after the MERS article was published on this website.

Traduz Google: versão em Português

1. A maioria dos casos atendidos até agora foram mais localizados na região Nordeste do Brasil, que responde por cerca de 12-15% do PIB; Considerando que, esta região tem cerca de 28% da população do país - que se conecta ao nível de renda, maior densidade populacional, nível de escolaridade e da pobreza, e por sua vez, higiene e saúde da mãe.

2. vírus Zika, embora não é o mesmo que o vírus da dengue, ainda vem sob a classe de vírus Flaviviridae, e pode ter algumas semelhanças com o vírus da dengue; Por essa razão, as recomendações de tratamento para o vírus da Dengue seguido poderia funcionar para o vírus Zika também.

3. O vírus da dengue, se não tratada adequadamente pode resultar em DHF; da mesma forma, pode haver uma ligação a microcefalia no recém-nascido; pode ser, tratamento da febre da mãe imediatamente usando o acetaminofeno / paracetamol juntamente com a ingestão suficiente de líquidos complementada com a saúde geral da mãe através de alimentação adequada pode reduzir a probabilidade de recém-nascidos recebendo condição congênita, microcefalia, que faz com que o desenvolvimento cerebral prejudicada, e tamanho da cabeça menor do que o normal .

Traductor Google: Versión española

1. La mayor parte de los casos vistos hasta ahora estaban más localizada en la región del noreste de Brasil, que representa alrededor del 12-15% del PIB; mientras que, esta región tiene alrededor de 28% de la población del país - que conecta con el nivel de ingresos, el aumento de la densidad de población, nivel de educación y la pobreza y, a su vez, la higiene y la salud de la madre.

2. virus Zika, aunque no es el mismo que el virus del Dengue, todavía viene bajo la clase de virus Flaviviridae, y podría tener algunas similitudes con el virus Dengue; Por esa razón, las recomendaciones de tratamiento seguidos por el virus del dengue podría funcionar para el virus Zika también.

3. El virus del dengue, si no se trata adecuadamente puede dar lugar a dengue hemorrágico; de la misma manera, puede haber una conexión a microcefalia en el recién nacido; puede ser, el tratamiento de la fiebre de la madre inmediatamente usando acetaminofén / paracetamol junto con la ingesta suficiente de líquidos junto con la salud general de la madre a través de una alimentación adecuada podría reducir la probabilidad de conseguir nueva condición congénita nacido del desarrollo del cerebro deteriorado, y la cabeza más pequeña debido a la microcefalia.

Findings

-> 1. Most of the cases seen until now were more localized in the Northeastern region of Brazil, which accounts for around 12-15% of the GDP; whereas, this region has around 28% of the country's population - which connects to income level, higher population density, educational level and poverty, and in turn, hygiene, and health of the mother. 

-> 2. Zika virus, though is not the same as Dengue virus, still comes under the flaviviridae class of viruses, and might have some similarities with Dengue virus; For that reason, treatment recommendations followed for Dengue virus might work for Zika virus too.

-> 3. Dengue virus, if not treated properly can result in DHF; in the same way, there may be a connection to microcephaly in the new born; may be, treating mother's fever immediately using acetaminophen/paracetamol along with sufficient intake of fluids combined with mother's overall health through proper nourishment might reduce the likelihood of new born getting congenital condition of impaired brain development, and smaller head due to microcephaly.

-> GEOSPATIAL MAPPING FOR DENGUE OUTBREAK IN BRAZIL

After writing the above section, we came across several highly relevant articles to further support our observations/inferences. To start with, here is an interesting poster published by Kelly Duncan at Tufts University 

(Link: https://sites.tufts.edu/gis/files/2013/11/Duncan_Kelly.pdf). To relate our analysis with Duncan's work, we have included that poster part of this article -

Dengue Outbreak Analysis: Duncan, K

The gadget spec URL could not be found

Analytics

If you were to look at the maps corresponding to dengue outbreak based on seasons, biomes, and climatic conditions in the above presentation, you would expect the spread of zika virus through mosquitoes, and its potential impact to be more dispersed rather than localized in the Northeastern part of Brazil. For the reason that the recent initial cases of "zika" based microcephaly appears to be more prevalent in the Northeastern Brazil , maternal nourishment, availability and accessibility to quality health care, and level of education of the common masses on top of population density should also be playing a role for a more localized number of microcephaly cases (For outbreak data, see below).

WHO DATA

-> WHO DATA - November 17th, 2015

As of 17 November, a total of 399 cases of microcephaly were being investigated in seven states in the northeast of Brazil. Most of the cases were registered in Pernambuco state (268). 

Other states that reported microcephaly cases are Sergipe (44), Rio Grande do Norte (39), Paraiba (21), Piaui (10), Ceara (9) and Bahia (8).


-> WHO DATA - November 21st, 2015

Pernambuco - 487 cases; Paraíba - 96 cases; Sergipe - 54 cases; Rio Grande do Norte - 47 cases; Piauí - 27 cases; Alagoas - 10 cases; Ceará - 9 cases; Bahia - 8 cases; Goiás - 1 case; One fatal case was reported in the state of Rio Grande do Norte [2].

-> CLEVELAND CLINIC INFORMATION

To further support this inference, it would be useful to present causation information pertaining to microcephaly (extracted from Cleveland Clinic website):

What causes microcephaly?


  • -> Chromosomal disorders such as Down’s syndrome, Cri du chat syndrome, Trisomy 13, and Trisomy 18
  • -> Maternal viral infections such as rubella (German measles), toxoplasmosis, and cytomegalovirus
  • -> Maternal alcoholism or drug abuse
  • -> Maternal diabetes
  • -> Mercury poisoning
  • -> Uncontrolled maternal PKU
  • -> Maternal malnutrition

The growth of the skull is determined by the expansion of the brain. Microcephaly occurs most often because the brain fails to grow at a normal rate. This can be caused by a variety of conditions or exposure to harmful substances during fetal development. Some of these causes include:

Acquired microcephaly might occur after birth due to various brain injuries such as lack of oxygen or infection.

Analysis Continued ->

The below table further supports connection between population density, per capita income, poverty rate to spread of mosquito-borne diseases.

Poverty Rate & Per Capita Income based on Regions
Table 1: Income, Income per capita & Poverty Rate for Brazilian regions -

 Regions Income Income Population Population Per Capita Income Per Capita Income Poverty Rate
 Year 1970 2010 1970 2010 1970 2010 2005
 North 2.94.7 4.4 8.3 65.6  69.2 25.6
 North East14.6  15.830.2  27.848.3  61.5 42.6
 South East 62.252.7 42.8 42.1 145.5 149.5  12.5
 South 16.117.9 17.7 14.4 90.8  113.1 11.1
 Center-West 4.2 8.9 4.9 7.486.1 117.0  15.0

Vaccination coverage and SES

Though the data presented in the below 2013 Barata et al. titled, Social Inequalities and Vaccination Coverage in the city of Salvador, Bahia, might not be current, the extent of vaccination (such as MMR) in Northeastern Brazil over the years, especially in lower SES regions appears to be below the norm compared to rest of the country. Moreover, in the same article, the authors have pointed out the following in their "Conclusions & Recommendations" section, which further strengthens the connection between poverty rate, education, maternal nourishment, extent of immunity, availability of quality health care all potentially playing a role in aggravating the current outbreak. Note: This article also shares useful information on the extent of immunization in various parts of the world.

 Section extracted from the above-mentioned article

"Although the national immunization program guarantees the acquisition of vaccines and their supply without direct costs for the population, there are social inequalities and differences in the use of such vaccines. The fact that children belonging to poorer socioeconomic strata have lower coverage emphasizes: the need for more accurate territorial location or an increase in the primary health care service network; and the use of new strategies to universalize access.

The World Health Organization defines a set of strategies to increase vaccination coverage. The first strategy is the increase in the supply closer to the community through the work of health community agents and educational activities. The second strategy recommended by the WHO is the dissemination of information through mass communication campaigns, participation of NGOs and guidance provided by health professionals when individuals are in contact with health services. The third strategy includes the change in health service practices, seeking to improve quality with the reduction in the number of abandonments and missed opportunities, use of reminders for the parents, home visits and other continuous monitoring and follow-up actions. Finally, the fourth strategy is associated with new administrative practices, including vaccination promotion and coverage monitoring through routine surveys 35 ."

Measles Outbreak & MMR Vacccination: Why this information on MMR vaccination relevant for this microcephaly outbreak, & What can be done? (This section is for Virologists)

In addition to the current "Zika" virus outbreak, there was also a measles outbreak between 2013 & 2015 in Brazil, especially impacting sections of Northeastern Brazil. With Zika virus being a ssRNA virus similar to MMR viruses, and moreover is a positive sense RNA virus similar to Rubella (though they are flavivirus and togavirus respectively), it would be worthwhile to see the level of MMR vaccination in this region, and its relationship to microcephaly. It is known that Rubella virus can also cause microcephaly in newborns, and hence, getting this data could be useful in coming up with a stop-gap option, especially considering a Zika virus vaccine might take several years to come to fruition. Moreover, we need to be certain about Zika virus playing a role in the microcephaly cases; Otherwise, Zika vaccine, if we were to have one, would become inconsequential in preventing microcephaly cases.

What else can be done?

Immediate administration of MMR vaccination (on a need basis) among masses in most affected regions might help in building immunity (if necessary, which appears to be the case based on the literature), along with prescribed WHO/CDC treatment recommendation similar to dengue (namely, acetaminophen with significant level of fluids, and proper nourishment) could help in somewhat addressing this global problem.

Note: Unlike Dengue, the recent outbreak appears to have a lesser impact on the mother/adults (or, in other words, the symptoms are milder) compared to its impact on the foetus, which could further be complicating the issue. It would be advisable to create awareness among the population about the importance of following the prescribed treatment recommendation as soon as the mother gets mild fever, and rash.

Questions to Answer ->

1. How about Alcoholism playing a role in these Microcephaly cases?

2. Is Education playing a role? 

3. Can it be due to GMO mosquitoes?

4. Can it be due to Tdap vaccine?

5. What is the real number of Microcephaly cases from this outbreak?

Updated with further information - May 1st, 2016


Total Number of Child Births & Microcephaly Incidence rate: 

TABLE: BRAZILIAN LIVE BIRTH INFORMATION SYSTEM
 YEAR LIVE BIRTHS INCIDENCE OF MICROCREPHALY CALCULATED CASES OF MICROCEPHALY
 2015 2,954,000 5.7/100000 168
 2015 2,954,000 5.5/100000 162
 2014 2,983,000 5.7/100000 170
 2014 2,983,000 5.5/100000 164
 2010 3,079,000 5.7/100000 176
 2000 3,664,000 5.5/100000 202


TABLE: OTHER PUBLIC HEALTH AUTHORITIES
 YEAR LIVE BIRTHS INCIDENCE OF MICROCREPHALY CALCULATED CASES OF MICROCEPHALY
 2015 (A) 2,954,000 20 591
 2015 (A) 2,954,000120 3,545
 2014 (A) 2,983,000 20 597
 2014 (A) 2,983,000 120 3580
 2015 (B) 2,954,000 28.5 842
 2014 (B) 2,983,000 28.5 850

TABLE - MICROCEPHALY PRODUCED BY INFECTIONS
 YEAR Toxoplasmosis based Congenital Cytomegalovirus - 10%Congenitil Cytomegalovirus - 15%  Min.
cases
Max. cases 
 2015 1034 1691 2536 2725 3570
 2014 1044 17072561 2752 3605
 2013 1053 1722 2584 2776 3637
 2012 1062 1737 2605 2799 3667
 2010 1078 1762 2644 2840 3721
 2000 1282 2097 3146 3380 4428

OTHER FACTS:

As per Feb 5th, WHO REPORT: Approx. 63% of the 1113 reports have been discarded as incorrect microcephaly diagnoses.


Conclusions from this WHO data set published on February 8th, 2016:

1. Though not overwhelmingly conclusive, Brazil's microcephaly issue appears to be a regularity, and can be influenced by a multitude of factors as mentioned above. In addition to those factors, this WHO report also brings in the impact of cytomegalovirus and toxoplasmosis on microcephaly cases.

2. Further, out of the 1100+ reports diagnosed, 63% of the cases appear to be misdiagnosed for microcephaly cases.

Moreover , factors such as food adulteration can play a significant role (as was the case with some studies suggesting higher levels of Pb, Cd in certain food products in Brazil) in causing microcephaly, especially in malnourished individuals.

By the way, what could be the potential connection between fever of mothers, and microcephaly?

Increased body temperature along with mother's overall health could potentially limit O2 supply to foetus resulting in reduced brain growth, causing microcephaly. More detailed analysis will be presented soon.

Other questions from above:

There were activists posts suggesting complications from Tdap vaccine, and GMO based mosquitoes potentially being the reason. Though the data set presented here need not directly negate the claims, we can deduce from the above data set that there are other primary proven reasons that could be connected to such level of incidence rate in microcephaly cases in Brazil, and even Zika may not be directly connected to the recent outbreak of microcephaly cases in Brazil.

References:

1. Bulletin of the WHO; Type: Research in emergencies Article ID: BLT.16.171223

2. www.ncbi.nlm.nih.gov/pubmed/9140346 & 9397045 (Malnutrition & Microcephaly in Australian Aboriginal Children)


QUESTIONS TO BE ANSWERED STILL:

- Educational level & its connection to microcephaly cases
Alcoholism & microcephaly cases

- What is Self-sabotage?


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