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Kenkyu Journal of Epidemiology & Community Medicine ISSN : 2455-4014
Data Guided Unraveling of Mysteries in Zika Virus Incidences
  • Shanmugam R*

    School of Health Administration, Texas State University, San Marcos, TX 78666, USA, E-mail: rs25@txstate.edu

Received: 22-02-2016

Accepted: 24-02-2016

Published: 26-02-2016

Citation: Shanmugam R (2016) Data Guided Unraveling of Mysteries in Zika Virus Incidences. J Eped Comed 2016: 100112

Copyrights: © 2016 Shanmugam R

Abstract

The Zika virus based illness is a nightmare to healthcare professionals, government agencies, community medical practitioners, travelers, residents of mosquitos’ abundant nations, and most importantly pregnant women. This article illustrates a genesis, incidence patterns, prevalence levels, adverse effects, and precautions to avoid Zika virus. Data about Zika virus are scattered in the literature. After collecting and analyzing such data in the public domain, incidence patterns of Zika virus illness are demystified in this article with comments in the end.
 
 

Keywords: Infectious Disease; Sexual Transmission of Virus; Clinical Trials; Epidemiology.
 

Introduction

What is Zika virus? It is a mosquito bitten flavivirus which triggers yellow fever, Japanese encephalitis, dengue, West Nile among others [1, 5, 6, 10, 15, 31, 33, 38]. Yellow fever is one of the few arboviruses with effective vaccines, which diminishes the risks of


 
Contracting the disease [2, 23, 35, 36]. Japanese encephalitis is prevalent in Southeast and East Asia


 
with an incubation period of 5 to 15 days [7, 9, 20]. Dengue virus is a deadly arbovirus in the world, causing more than 50 million infections per year and many deaths occur especially among children [3, 4, 13]. Zika virus is an antibody substance which enters a human body due to an injection by day-time biting mosquitoes. Zika virus exists with a low titer of antibodies: IgM and IgG at early phase of infection [8].

 

 

Figure 1. Aedes mosquito

 

Zika virus spreads in a pool of stagnant water as small as a bottle cap. Recently, thousands of humans have been infected in dense forest surrounded areas of Brazil. The World Health Organization (WHO) has been alarmed by the spread of Zika virus and warns international travelers in general and pregnant women in particular to be cautious to use full cover of the body from Aedes mosquitoes (see Figure 1) and seek immediate medical help if acquired the virus. When a pregnant woman contracts the Zika virus, the baby might get birth defects including microcephaly (which is a neuro developmental disorderstate with shrunken head and/or brain size as shown in Figure 2) [16, 29]. The symptoms of Zika virus are rashes, headache, fever, joint pain, red eyes etc. See Table 1 for sample results pertaining to the victims in Brazil during 2015. 


A difficulty is that there is no widely available and accepted unique diagnostic lab test for Zika virus infection. In terms of symptoms, Zika virus is closely related to dengue and yellow fever. Consequently, the lab test results or symptoms are confounded with that of yellow fever and dengue. See Figure 3 for details about the prevalence of these competing viruses worldwide.

 

 

 

Figure 2. Evidence of microcephaly.

 

 

Figure 3. Prevalence of competing viruses worldwide (www.cdc.gov)

To detect Zika virus, a blood, serum, urine, or tissue sample of the mosquito bitten victim must be sent to an advanced laboratory test for its molecules in the first week of symptoms. As of now, there is no known antiviral medication to disinfect Zika virus except providing nourishment, avoiding mosquito bites by staying in screened or air-conditioned rooms, sleeping under mosquito nets, wearing insect repellent at all times, wearing long pants, long sleeves, shoes and hats, according to Center for Disease Control (CDC). 


Zika virus does not spread by touching or hugging an infected person. However, it was


Suspected first and is now confirmed that Zika virus is sexually transmitted.
 
In 2008, a scientist studying malaria in Africa returned to Colorado [19] and got infected his wife before developing symptoms himself. Both husband and wife exhibited first fever, rash and headaches. Their blood test revealed that both had had Zika virus. In 2013, Zika virus was found in the semen of a 44-year-old Tahitian man.


In February 2016, an international traveler who returned to Dallas, Texas from Venezuela apparently had infected a sexual partner. Now, the Center for Disease Control (CDC) made a public warning that those who return from Zika virus geography should use condoms before sexual activities.


Medical researchers are now working hard to formalize an effective drug and/or an efficient treatment for Zika virus cases. For an example, a microbiologist Dr. Sowmya Swaminathan revealed in the first week of February 2016, that the Indian Medical Research Council has devised successfully a vaccination for Zika virus and it would be released to the market after a patent is received.


Compiling and then analyzing the publically available Zika virus data, this article demystifies the patterns of virus in nations around the world. A few comments are stated in the end.

 

2. Genesis of Zika Virus 


Why this virus is named Zika virus? The earliest incidence of Zika virus was noticed about seventy years ago among monkeys in 1947 near what is geographically called Zika forest in Uganda. The word zika means “overgrown” in the Luganda language.
 
In 1951, first human with Zika virus was identified and got isolated in Uganda [18, 37]. Zika virus peaks in rainy seasons (June to August) and lows in dry seasons (January to February).
 
In 1975, Zika virus was detected in Ibadan, Nigeria. During 1977 to 1978, Malaysia and Indonesia witnessed clusters of Zika virus in rainy season. In June 2007, Zika virus appeared in Yap State of Micronesia. Zika virus infections were detected among people in Brazil which are displayed in Table 1. The data in Table 1 are analyzed and interpreted in Section 3 of this article.
 
As of 1 December 2015, nine nations in the North and South American continents have confirmed Zika virus and they are: Brazil, Chile (on Easter Island), Colombia, El Salvador, Guatemala, Mexico, Paraguay, Suriname, and Venezuela.


Within Brazil, a total of 18 states have confirmed Zika virus cases. As of 30 November 2015, about 1,248 cases of microcephaly, including 7 deaths, are reported in 14 states of Brazil. How common is microcephaly in Brazil? About 150 cases of microcephaly occur usually in a year in Brazil. But, nearly 4,000 microcephaly babies are identified in just 2015 alone. See Table 2 for the unusual incidences of microcephaly in Brazil and they are clinical evidences of the impact of Zika virus. The data in Table 2 are further analyzed and interpreted in Section 3.

 

# PCR [17] result for Zika virus

Mean (standard deviation) age

# with rash

# with fever

# with Myalgia

# with headache

Total

(+)

33(15)

6

3

4

3

16

(-)

31(8.5)

12

6

9

11

38

Sum

 

18

9

13

14

54

 

 

 

Table 1: Outcomes of 24 patients with lab test result for Zika virus in Brazil during 2015 (www.cdc.gov/eid) [12, 34]

 

 

 

State in Brazil

Annual # live births (LB)

During 2010-2014 number of microcephaly per 1,000 LB (YB )

During 2015 number of microcephaly per 1,000 LB (YN)

Pernambuco

140264

0.06

4.61

Paraíba

47998

0.09

5.17

Rio Grande do Norte

47698

0.04

1.66

Sergipe

34477

0.05

2.23

Alagoas

44331

0.08

1.33

Bahia

211660

0.05

0.17

Piauí

48989

0.06

0.73

Ceará

128112

0.05

0.2

Rio de Janeiro

219876

0.06

0.06

Tocantins

24586

0.05

0.49

Maranhão

119069

0.03

0.1

Goiás

90559

0.03

0.02

Distrito Federal

43935

0.06

0.02

Mato Grosso do Sul

41421

0.02

0.02

 

 

 

Table 2: Microcephaly cases per 1 000 live births (LB) reported in the fourteen Brazilian states during 2010–2014 versus just in 2015 Source: (Ministério da Saúde (Brazil), 2015)

 

 

3. Data Guided Demystification of Zika Virus
 
The following assertions are based on the data in Table 1 and the results in Shanmugam [32]. The Figure 4 depicts that the Zika virus is a smaller subset compared to that of yellow fever, Japanese encephalitis, and Dengue virus. The epidemiologic measure prevalence is the probability Pr(Symptom  Zika_Virus) of acquiring Zika virus. An estimates prevalence of Zika virus among those who take the lab test is 30% which is not negligible for healthcare professionals to ignore.


The sensitivity (Se) is the conditional probability Pr(Symptom Zika_Virus). If one has the Zika virus, the sensitivity (Se) for the symptoms like rash, fever, myalgia, or headache is respectively only 38%, 19%, 25%, and 19%.  Among the symptoms, the most serious and true symptom is the rash for the Zika virus. The specificity (Sp) is one minus the conditional probability

 

 

 

The specificity (Sp) to no rash, no fever, no myalgia, or no headache for those without Zika virus (that is, for healthy people) is respectively only 68%, 84%, 76%, and 71%. In other words, not all people who do not have Zika virus show no symptom of rash, fever, myalgia, or headache. The most deceptive one is no fever symptom to think that the person is safe from Zika virus.


The positive predictive likelihood (PPL) is the conditional probability

 

 

The positive predictive likelihood (PPL) of symptom rash, fever, myalgia, or headache to think that the person has Zika virus is only 33%, 33%, 31%, or 21% respectively. The least predictive symptom is the headache and the healthcare professionals ought to know about it.

 

Country

Longitude (+ means west and – means East)

Latitude (+ means north and – means south)

Land area in 1,000 square miles

Percent of water area

Population size in million

# Zika cases

Barbados

59

13

166

0

0.2

3

Bolivia

63

-17

424

1.29

11

1

Brazil

47

-15

3287

65

204

4000

Cambodia

-104

11

181

2.5

15

1

Canada

75

45

3854

8

35

4

Colombia

74

4

440

8.8

42

98

Dominican

70

19

18

70

9

8

Ecuador

78

-0

275

5

15

6

El Salvador

89

13

8

1.4

7

3

Guatemala

90

14

108

40

14

1

Guyana

58

6

214

8.4

0.7

1

Haiti

72

18

10

70

10

5

Honduras

87

14

43

0

8

2

Indonesia

-106

-6

735

4.85

255

9

Malaysia

-101

3

329

0.3

30

1

Mexico

99

19

761

2.5

112

3

Panama

79

8

29

2.9

4

3

Paraguay

57

-25

157

2.3

6

6

Philippines

-120

14

300

61

102

1

Puerto Rico

66

18

3.5

1.6

4

1

Suriname

55

5

63

1.1

0.5

6

Thailand

-100

13

513

0.4

68

10

USA

77

38

3,794

7

321

31

Venezuela

66

10

353

32

27

7

 

 

Table 3: Number of Zika virus cases since April 2015–January 2016 [9, 11, 12, 14, 18, 20-22, 24- 28, 30].

 

The negative predictive likelihood (PPL) of lack of symptom: no rash, no fever, no myalgia, or no headache to think that the person is healthy without Zika virus is only 33%, 13%, 22%, or 28% respectively. The best comforting no symptom is no rash and the healthcare professionals ought to realize it. In essence, rash is a warning symptom for Zika virus and this data guided clue should help the community medical practitioners.

 

The optimal diagnostic symptom [32] for those with the Zika virus would have to be the largest Youden index  and it is 0.06, 0.03, 0.01, and -0.1 for rash, fever, myalgia, and headache respectively. Notice that all these symptoms do significantly differ from each other. However, rash is the optimal symptom and the deceptive symptom (because of the negative value for Youden index) is headache for the Zika virus. 

  

 

 

  

 

 

Figure 4: Relative incidences of Zika, yellow fever, Japanese encephalitis, dengue viruses

 

The occurrence of microcephaly is a serious medical menace to the public health professionals and community medical practitioners as much as to the pregnant women. See Table 2 for the number of microcephaly cases per 1 000 live births (LB) reported in the fourteen Brazilian states during 2010–2014 versus just in 2015, according to Ministério da Saúde (Brazil, 2015). The annual number of live births (LB) in Brazil ranged from 24,596 to 219,876 in this period 2010-2015. But, the number of microcephaly cases per 1,000 LB ranged from 0.02 to 0.09 up to 2014 but it was escalated to 0.02 to 5.17 in 2015 due to Zika virus in an uneven manner among the fourteen states in Brazil. The outliers are Paraiba and Pernambuco states in Brazil. At a fixed number of LB, the partial correlation between the number of microcephaly in 2014 and that in 2015 is 0.58 with a significance level 0.03 as its p-value. A

Predictive regression of the number (  ) of the number of microcephaly in 2015 should be                     

 

Where is  the number of microcephaly cases in 2014. This suggests that the annual LB is not a factor but surely the microcephaly cases in 2015 will increase by an amount 52.2 per microcephaly case in 2014. This is a too strong warning to the public health agencies. There is a closer proximity for the microcephaly incidence in 2015 with the microcephaly incidence of 2014 but not to the annual LB as it is depicted in Figure 5.
Then, one wonders whether Zika virus occurs in geographic clusters on earth. For this purpose, the number of Zika viral cases in twenty-four small to large countries along with their population size, land area in 1,000 square miles, the percent of water area in the country, longitudinal and latitudinal locations are compiled in Table 3.


The correlation, 0.61 between the number of Zika virus cases and the land area (in 1,000 square miles) is significant (with p-value = 0.002). The correlation, 0.42 between the number of Zika virus cases and the percent water area is significant (with p-value = 0.04). The correlation, 0.465 between the population size and the land area (in 1,000 square miles) is significant (with p-value = 0.026). The correlation between the population size and the percent water area is insignificant.

By controlling the population size, the partial correlation, 0.483 between the number of Zika virus cases and the land area (in 1,000 square miles) is significant with p-value of 0.023. It suggests that the Zika virus cases are likely to be more in a large land area irrespective of the density of population in the area or the percent of water area. The projection ( ) of the number of Zika virus cases increases as the location moves up in latitude, as the land area increases, and as the percent of water area increases, according to a regression fit

 

Whose coefficient of determination is 

 

A principal component analysis would identify the closeness of the factors and the clusters of countries with respect to Zika virus. This is done. A principal component analysis (with 62% cumulative percent of variation explained) of the international data in Table 3 reveals (see Figure 6) that the number of Zika virus cases is in closer proximity with the land area, percent water area but is at a distant proximity with the population size. No meaningful proximity exists between the number of Zika virus cases and the latitude or longitude of the geographic location. Furthermore, there are three clusters of countries with respect to the Zika virus cases, as they are identified in Figure 7. The first cluster consists of countries Barbados, Paraguay, Guyana, Ecuador, Venezuela, Bolivia, Mexico, Canada, Columbia, USA, Brazil, Indonesia, Thailand, Malaysia, Philippines, and Cambodia. The second cluster consists of countries Surinam, Guatemala, Honduras, and Panama. The third cluster consists of countries El Salvador, Puerto Rico, Haiti, and Dominican.  

 

 

 

 

Figure 5: Proximity among annual LB, microcephaly in 2014 and 2015.

 

 

 

 

 

Figure 6: Proximity among the number of Zika virus cases, latitude, longitude, land area, percent water area, population size

 

 

   Figure 7: Clusters of countries with respect to the Zika virus.

 

 

Comments and Conclusions

A penalty for humans to pay for enjoying the benefits due to living in an era of gene altered seeds and farming is perhaps to encounter unknown viruses and diseases with their fatal consequences such as Zika virus. No one really knows, at this stage, the cause of Zika virus. There is an unconfirmed rumor among the residents in Brazil that those who provided gene manipulated fertilizers to the farmers are really responsible for the mosquitoes to develop mutations in their genes and it caused the Zika virus. However, microbiological and genetic researchers are now fully engaged towards a discovery of remedial medicine and treatment of the Zika virus. In fact, Dr. Sowmya Swaminathan announced in the first week of February 2016 that the Indian Medical Research Council has successfully discovered a vaccination for Zika virus and the medicine would be soon released to the market after a patent is received. A hope is now raising among epidemiologists and community medical Practitioners that the menace of Zika virus would soon be a historical thing of the past.   

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