The Next Vaccine For Pregnant Women

In case you hadn’t heard, there’s a new vaccine that will likely be marketed toward pregnant women within the next couple of years. It’s for Respiratory Syncytial Virus (RSV) in the newborn – a common cold-like illness that is usually mild in healthy people. Nearly all children will have had an infection by their second birthday – according to the CDC. Of those who have an infection before 6mths of age, approximately 1-2% will be hospitalised, due to complications such as bronchiolitis or pneumonia [1].

The quest for an RSV vaccine actually began decades ago…and it had disastrous beginnings.

In the early 1960’s, an RSV vaccine, propagated on human embryonic kidney cells, then passaged through monkey cells, before being inactivated with formalin, and adjuvanted with aluminium, was trialled on infants, with disastrous results. Up to 80% of vaccinated infants were hospitalized with severe lower-respiratory infections, and two babies died [2].

It took nearly four decades to figure out why the vaccine had such tragic results – which just goes to show how little is understood about the very system they seek to tamper with. It was due to “Lack of antibody affinity maturation followed poor Toll-like receptor stimulation”, according to the paper, published in Nature journal, in 2009 [3].

The quest for an RSV vaccine resumed with gusto.

At the forefront of the charge for an RSV vaccine, is Novavax, a biotechnology company with several products currently in the clinical testing stages. Following the announcement of positive results of Phase 2 clinical trials in older adults, in 2015, CEO of Novavax, Stanley Erck declared their RSV vaccine could be “the largest selling vaccine in the history of vaccines in terms of revenue” [4].

Unfortunately, the Phase 3 trial in older adults failed to show efficacy, and the company lost more than $1.5 billion in market value within hours of the announcement, as disappointed investors pulled their money [5].

This gives us some idea of the immense pressure faced by companies to come up with the next new ‘blockbuster’ vaccine. For a company like Novavax, with no products on the market yet, (just the potential of new products), investor confidence is necessary to finance the lengthy clinical trial and regulatory approval process.

Novavax then turned their attention to pregnant women, and in February 2019, announced favourable results (actually, not as favourable as they were hoping for, but nevertheless, they found a way to put a positive spin on them) from a Phase 3 clinical trial on pregnant women. The vaccine, called ‘Resvax’, is not only aluminium adjuvanted, it is also genetically-engineered with nano-particles. The press release stated “Our next steps include meeting with U.S. and European regulators to review these data and to discuss the path forward for licensure” [6].

The trials on pregnant women were funded, in part, by an $89 million grant from the Bill and Melinda Gates Foundation, with the stated purpose “to advance to WHO Pre-Qualification the development of a respiratory syncytial virus (RSV) vaccine for maternal immunization to reduce the burden of RSV disease in infants less than six months of age in developing countries” [7-8].

Obviously, the burden of RSV disease falls mainly on developing nations, however, it’s likely that a new RSV vaccine will also be targeted at pregnant women in western countries.

One of the important ways to prevent respiratory disease in infants is via breastfeeding. A study published in British Medical Journal found that among 115 babies who had been hospitalized for RSV infection, only 8 were breastfed [9].

Given that breastfeeding rates are vastly lower in developing countries, I can’t help but wonder why $89 million (and more) wasn’t spent to increase maternal nutrition and breastfeeding rates? For example, in West/Central Africa, only a mere 20% of infants are exclusively breastfed for the first six months of their life [10].

One of the main groups promoting the need for an RSV vaccine during pregnancy, is the Oxford Vaccine Group, who note that almost all infant deaths due to RSV are in developing countries [11].

The director of Oxford Vaccine Group is Andrew Pollard, who holds several vaccine-related patents [12-13], and is Chair of the UK Department of Health’s Joint Committee on Vaccination and Immunisation, and the European Medicine Agency’s scientific advisory group.

Another member of the group, Matthew Snape, has been Principal Investigator in clinical trials of numerous RSV vaccine candidates. He is also the Director of the National Immunization Schedule Evaluation Consortium (NISEC) [14].

It is also interesting to note that the CDC has held a patent for an RSV vaccine, since 2010 [15]. How might that affect any future decisions regarding RSV vaccinations being promoted to pregnant women?

References:

[1] CDC, Respiratory Syncytial Virus Infection (RSV), https://www.cdc.gov/rsv/high- risk/infants-young-children.html. Accessed March 2019.

[2] Dudas RA, Karron RA. Respiratory syncytial virus vaccines. Clin Microbiol Rev. 1998;11(3):430-9.

[3] Delgado MF, Coviello S, Monsalvo AC, et al. Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease. Nat Med. 2008;15(1):34-41.

[4] FierceBiotech, Novavax craters after phase III RSV F vaccine failure; seeks path forward, https://www.fiercebiotech.com/biotech/novavax-craters-after-phase-iii-rsv-f-vaccine-failure- seeks- path-forward. Accessed March 2019.

[5] CNBC, Novavax is down 80%. Here’s why its been really hard to develop an RSV vaccine, https://www.cnbc.com/2016/09/16/heres-why-its-been-really-hard-to-develop-a-vaccine-for- rsv.html. Accessed March, 2019.

[6] Novavax, Press Release: Novavax announces topline results from Phase 3 PrepareTM Trial of Resvax TM for prevention of RSV disease in infants via maternal immunization, http://ir.novavax.com/news-releases/news-release- details/novavax-announces-topline-results-phase-3-preparetm-trial. Accessed March 2019.

[7] Novavax, Bill & Melinda Gates Foundation, https://novavax.com/page/19/bill-and- melinda-gates-foundation. Accessed March 2019.

[8] Bill and Melinda Gates Foundation,How We Work, Grant: Novavax, Inc, https://www.gatesfoundation.org/How-We-Work/Quick-Links/Grants- Database/Grants/2015/09/OPP1127647. Accessed March 2019.

[9] Downham MA, Scott R, Sims DG, Webb JK, Gardner PS. Breast- feeding protects against respiratory syncytial virus infections. Br Med J. 1976;2(6030):274-6.

[10] UNICEF Progress for Children, Nutrition Indicators: Exclusive Breastfeeding, https://www.unicef.org/progressforchildren/2006n4/index_breastfeeding.html. Accessed March 2019.

[11] Oxford Vaccine Group: Vaccine Knowledge Project, Respiratory Syncytial Virus, http://vk.ovg.ox.ac.uk/rsv. Accessed April 2019.

[12] Justia Patents, Vaccine, https://patents.justia.com/patent/20130089571, Accessed April 2019.

[13] Justia Patents, Compositions comprising OPA Protein Epitopes, https://patents.justia.com/patent/20100183676. Accessed April 2019.

[14] Oxford Vaccine Group, Matthew Snape, https://www.ovg.ox.ac.uk/team/matthew-snape. Accessed April 2019.

[15] Anti-RSV Immunogens and methods of Immunization, https://patents.google.com/patent/US8846056?oq=vaccine+inassignee:centers+inassignee:f or+inas signee:disease+inassignee:control. Accessed April 2019.

The Truth About Vaccines & Other Drugs in Africa

There seems to be a perception in the Western world that African children are dying due to lack of vaccines, but is that actually true? Not exactly.

In many cases, the relentless push for vaccines (usually by outside interests) as a magic fix for disease, has come at the expense of other interventions.

According to UNICEF statistics, Rwanda has 95% – 98% vaccination coverage for diptheria-tetanus-pertussis…yet 37% of children are stunted due to malnutrition. Only 62% have access to proper sanitation [1]

Botswana has 95% children vaccinated with three doses of diptheria-tetanus-pertussis vaccine…but just over half receive Vitamin A supplementation (lauded in the early 1990’s as THE most effective health intervention of all), and only 20% of infants are exclusively breastfed [2].

Malawi is ranked 9th poorest country in the world, with more than half its people living below the poverty line, 9.6 million Malawians (more than half the population) don’t have access to a decent toilet, 5.6 million people (1 in 3) don’t have access to clean water, and 42% of children are stunted [3], yet more than 80% of children are up-to-date with vaccinations…[4].

The Malawi vaccination schedule now includes vaccines for measles, polio, cervical cancer, rotavirus, pneumococcal disease, diphtheria, tetanus, pertussis, hepatitis B, Haemophilus Influenza type B (Hib) [5].

According to UNICEF, almost 90 percent of child deaths from diarrhoeal diseases are directly linked to contaminated water, lack of sanitation, or inadequate hygiene [6], but money that may have been spent on sanitation and procurement of clean water, is spent on rotavirus vaccines instead.

Also, recall that the diptheria-tetanus-pertussis vaccine used in poor African countries is likely the old whole-cell thimerosal-containing vaccine, due to being cheaper than the new acellular vaccine [7].

African countries are increasingly rolling out HPV vaccination campaigns for school-girls. While it’s true that the majority of cervical cancer cases are in developing countries, one can’t help but wonder if HPV vaccination is a wise use of resources, given the more pressing needs in many sub-saharan countries.

In 2011, Merck donated 2 million doses of Gardasil vaccine to Rwanda, and 95% of the nation’s 11-year-old girls were vaccinated. The freebies ran out after three years, at which time Merck offered the vaccine to the Rwandan government at ‘discount prices’. Such donations can have the effect of locking governments into programmes which they later have to fund themselves, at the expense of more pressing issues, and may be more about ‘priming the market’, than charity on the part of the drug company [8-9].

Between 2013 – 2016, 26, 766 young girls in Malawi were given quadrivalent HPV vaccination as part of a pilot project, supported by GAVI – and 2051 girls who participated were under the age of 9 [10].

Vaccination coverage in Tanzania in 2014 for school and out of school girls was estimated at 93 per cent and 92.6 per cent, respectively. The chief Health Minister boasted that, despite “heartbreaking stories of the ill effects of vaccines” online, Tanzania had not even registered one single adverse reaction from the vaccine [11]. Is there an incentive for African governments – hopeful of foreign investment from pharmaceutical companies to downplay risks and reactions, in order to keep up the flow of income?

In December 2012, 500 children in Chad received a new experimental meningitis vaccine, and 38 children were later hospitalized, with 7 of the children flown to Tunisia for specialized treatment. The Chadian government declared their “state of health is not worrying”, but other sources in Chad claimed the children were paralysed [12-13].

In 2008, the Center for Research on Multinational Corporations reported (among others) the case of clinical trials in Uganda between 1997 – 2003, where thousands of women suffered adverse reactions to the drug Nevirapine, and some died – and all of it went unreported, while testing continued [14].  

Supplemental Immunization Activities

In addition to routine childhood vaccines, WHO and other agencies also conduct ‘supplemental immunization activities’, which are mass vaccination campaigns that aim to administer extra doses of vaccines. According to the WHO, there have been “thousands of these supplementary vaccination campaigns” with oral polio vaccine since the 1980’s, with children vaccinated regardless of prior vaccine history. The extra doses were not recorded on the child’s health cards [15].

Extra doses of measles vaccines are also given. A quick look at the Measles and Rubella Initiative Calendar for 2019 shows they plan on supplementally vaccinating more than 100 million people in sub-Saharan Africa this year – in addition to routine vaccinations [16].

Experimental Vaccines

In addition to routine vaccinations and supplementary vaccination, poor African countries are increasingly used to test experimental vaccines because it’s quicker and cheaper and less stringent regulations than western countries “Development cycles can be reduced thanks to the faster recruitment of subjects from a larger pool of patients. The costs of recruiting patients and paying investigators are lower too” [17]

This poses some real ethical problems. I have never been to Africa but I have lived in a developing country, and witnessed first-hand the reverence given to those who are in positions of power, or overseas-trained. People are too embarrassed or intimidated to ask questions of their doctor or report side-effects, as it would seem disrespectful and ‘out of line’ with the societal and cultural hierarchy.

Other developing regions face similar issues. M. Nabeel Ghayur, a pharmacologist who worked in drug development in Pakistan says: “People actually have blind trust in their doctor in South Asia. They have no idea what drug development is, they have no idea what clinical trials are.

He said there was little red tape in those countries, and that people would rarely ask about drug side effects and legal issues” [18].

Starting next month (March, 2019), 750,000 babies in Kenya, Ghana and Malawi will be given a new experimental malaria vaccine. The vaccine Mosquirix will be given to children in four doses- at six, seven, nine and 24 months through an injection on the upper arm [19].

 The Star newspaper in Kenya reported: “Mosquirix, also called RTS,S, was first conceived in the 1980s and has undergone all clinical trials, returning less than optimal results.

The vaccine – made by GSK – is only effective in 30 to 50 per cent of patients, says the WHO.

Its effectiveness diminishes over time and it disappears fastest in children who are most exposed to malarial mosquito bites. However, because no defence against malaria is perfect, the vaccine is being considered in addition to the existing defences” [20].

GlaxoSmithKline and its backers, including Bill and Melinda Gates Foundation, had already spent $565 million on developing the drug, which brought back disappointing results in early testing, and did not meet the expected criteria for a malaria vaccine set out by a WHO-led consortium”, which requires a “protective efficacy of more than 50% against severe disease and death, and last longer than one year.” [21]

In 2017, the Global Task Force on Cholera Control launched a very ambitious set of goals, including 90% reduction in cholera deaths by 2030. Naturally, vaccines feature prominently, namely the oral cholera vaccine. A year later, the ‘largest vaccination drive in history’ took place, with over 2 million people vaccinated for cholera in Zambia, Uganda, Malawi, South Sudan and Nigeria [22].  

As of January 2019, more than 66,000 people in the Democratic Republic of Congo have been vaccinated with Merck’s V920, an experimental Ebola vaccine [23].

A Chinese-made genetically-engineered Ebola vaccine was given to 500 adults in Sierra Leone in 2015, as part of a Phase II trial. The Chinese FDA then approved the vaccine, without any Phase III trials [24].

In 2018, some 20,000 Malawian children were enrolled to receive an experimental typhoid conjugate vaccine [25].

Supplemental Drugs

In addition to routine vaccines, supplemental vaccines and experimental vaccines…many African children (and pregnant women) are also given supplemental drugs – malaria (sulfa) drugs, three times during the first year of life (starting from 10 weeks old), or several times per year during childhood – even if they have no infection [26]. During pregnancy, mothers are given the drugs at least three times during the 2nd and 3rd trimesters – again, even if they have no infection [27].

This is called “intermittent preventive therapy”, and it was promoted aggressively by the Bill and Melinda Gates Foundation, to the tune of at least $28 million dollars, with the establishment of the ‘IPTi Consortium’ [28].

in 2008, a technical advisory group at the World Health Organization (who coincidentally has received more than $2.4 billion in donations from the Bill and Melinda Gates Foundation, since 2000 [29], including a $1.2 million grant in 2006, with the express purpose of ensuring “that the IPTi consortium outcomes are collated, assessed by international experts, and result in a WHO policy recommendation” [30])  failed to recommend the program, due to concerns over safety and efficacy.

The protests from the Gates Foundation and their scientists were so loud and insistent, it prompted WHO malaria chief to write a memorandum (which was later leaked to newspapers) to WHO director, Margaret Chan, saying: “although it was less and less straightforward that the health agency should recommend IPTi, the agency’s objections were met with intense and aggressive opposition from Gates-backed scientists and the foundation…” [31]

Not to be deterred, the Gates Foundation then donated funds to have the Institute of Medicine conduct another review, chaired by a doctor whose work has received at least $50 million in funding from the Gates Foundation [32].

Predictably enough, the IOM review concluded that “an intervention with results of this magnitude is worthy of further investment as part of a public health strategy to decrease morbidity from malaria infections in infants“, although they noted that “time and resources did not allow independent audits of trial conduct, data management, or analysis” [33].

The WHO malaria chief who protested the excessive influence of the Gates Foundation, was later replaced…by a member of the Gates-founded IPTi Consortium (and now Vice-President of Johnson & Johnson pharmaceutical company [34]) and WHO then proceeded to recommend these sulphonamide drugs to infants ( given at the same time as routine vaccines for diptheria-tetanus-pertussis and measles), children and pregnant mothers, despite evidence of increasing drug-resistance in sub-Saharan Africa…

Prior to the IPTp and IPTi programs, pregnant women in malaria-endemic areas of Africa were given weekly doses of chloroquine, until drug resistance and compliance issues made it unfeasible to continue [35].

Other chemical exposures

The use of DDT to control mosquitos in malaria-endemic areas was endorsed by the World Health Organization in 2006, and its use has been increasing ever since. The chemical is sprayed inside homes and buildings – according to a report by the United Nations Environment Program, at least 3952 tonnes of DDT were sprayed in Africa and Asia in 2007 [36].

Agricultural spraying of DDT is common in Africa, especially in West Africa, where mosquitos have developed resistance to it [37].

The vast wealth of precious metals and natural resources in Africa have been both a blessing and curse to its people. Gold and other mining in Africa have produced countless mountains of toxic wastes that pollute the air, soil and water, most notably with uranium, arsenic and lead [38].

Another form of pollution experienced in poorer parts of the world, such as sub-Saharan Africa, is indoor air pollution from cooking over open fires, using wood, charcoal, kerosene or animal dung. The World Health Organization estimates that as many as 3.8 million people die prematurely every year, due to health conditions caused by indoor air pollution, the majority due to pneumonia [39].

References:

[1] UNICEF, Statistics: Rwanda https://data.unicef.org/country/rwa/. Accessed February, 2019

[2] UNICEF Statistics: Botswana, https://data.unicef.org/country/bwa/. Accessed February, 2019.

[3] WaterAid, Facts and Statistics: Malawi, https://www.wateraid.org/mw/facts-and-statistics. Accessed February, 2019.

[4] WHO, WHO and UNICEF Estimates of Vaccine Coverage, 2017 Revision, https://www.who.int/immunization/monitoring_surveillance/data/mwi.pdf, Accessed February, 2019.

[5] GAVI The Vaccine Alliance, Iceland pledges US $1 Million to Immunise Children in Malawi, https://www.gavi.org/library/news/statements/2019/iceland-pledges-usd1-million-to-immunise-children-in-malawi/, Accessed February, 2019.

[6] UNICEF, Press Release, Children Dying Daily Because of Unsafe Water Supplies and Poor Sanitation and Hygiene, New York: UNICEF, 2013.

[7] WHO, Biologicals: Pertussis, https://www.who.int/biologicals/vaccines/pertussis/en/. Accessed February, 2019.

[8] The Guardian, Drug donations are great, but should Big pharma be setting the agenda? https://www.theguardian.com/world/2013/apr/29/drug-company-donations-bigpharma. Accessed September, 2017.

[9] Editorial, Financing HPV vaccination in developing countries, The Lancet, 2011, 377(9777):1544.

[10] Msyamboza KP, et al, Implementation of a human papillomavirus vaccination demonstration project in Malawi: successes and challenges, BMC Public Health series, 2017, 17:599.

[11] AllAfrica, Tanzania: Cancer Vaccination Program Registers Success, https://allafrica.com/stories/201602152199.html, Accessed February, 2019.

[12] MedicalExpress, 38 children hospitalised after meningitis shot in Chad, https://medicalxpress.com/news/2013-01-children-hospitalised-meningitis-shot-chad.html#jCp. Accessed February, 2019][

[13] England C, Minimum of 40 children paralyzed after new meningitis vaccine, VacTruth, https://vactruth.com/2013/01/06/paralyzed-after-meningitis-vaccine/. Accessed February 2019

[14] Kelly S, Testing drugs on the developing world, The Atlantic, 27th February 2013, https://www.theatlantic.com/health/archive/2013/02/testing-drugs-on-the-developing-world/273329/. Accessed February, 2019.]

[15] Helleringer S et al, Supplementary polio immunization activities and prior use of routine immunization services in non-polio-endemic sub-Saharan Africa, Bulletin of the World Health Organization, 2012, https://www.who.int/bulletin/volumes/90/7/11-092494/en/. Accessed February, 2019.

[16] Measles and Rubella Initiative, SIA Schedule, https://measlesrubellainitiative.org/resources/sia-schedule/. Accessed February, 2019.

[17] Edwards M, R & D in Emerging Markets: A new approach for a new era, McKinsey & Company, 2010, https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/r-and-38d-in-emerging-markets-a-new-approach-for-a-new-era. Accessed February, 2019.

[18] Joelving F Many drugs for US kids tested in poor countries, Reuters, 23rd August 2010, https://www.reuters.com/article/us-drug-tests-idUSTRE67M1VO20100823. Accessed February, 2019.

[19] Kulkani P, Malaria Vaccine trials in Africa: Dark saga of outsourced clinical trials continues, Newsclick, March 2018, https://www.newsclick.in/malaria-vaccine-trials-africa-dark-saga-outsourced-clinical-trials-continues, Accessed February 2019.

[20] Muchangi J, Kenyan children to get first malaria vaccine in the world next month, The Star,14th February, 2019, https://www.the-star.co.ke/news/2019/02/14/kenyan-children-to-get-first-malaria-vaccine-in-the-world-next-month_c1894869. Accessed February, 2019.

[21] Kulkani P, Malaria vaccine trials in Africa: Dark saga of outsourced clinical trials continues, Newsclick, 17th March 2018, https://www.newsclick.in/malaria-vaccine-trials-africa-dark-saga-outsourced-clinical-trials-continues. Accessed February, 2019.

[22] UNICEF, Global Task Force on Cholera Control marks a year of progress toward ending cholera worldwide, https://www.unicef.org/press-releases/global-task-force-cholera-control-marks-year-progress-toward-ending-cholera. Accessed February, 2019.

[23] Ward Hackett D, Ebola vaccinations expanding in Central Africa, https://www.precisionvaccinations.com/v920-ebola-vaccine-now-deployed-drc-uganda-and-south-sudan. Accessed February, 2019.

[24] Liu A, China approves domestic Ebola vaccine developed from recent outbreak, FiercePharma, https://www.fiercepharma.com/vaccines/china-approves-self-developed-ebola-vaccine-from-2014-outbreak-virus-type. Accessed February, 2019.

[25] Gordon M, Trial kicks off in Malawi: First child vaccinated with typhoid conjugated vaccine in Africa, http://www.coalitionagainsttyphoid.org/trial-kicks-off-in-malawi-first-child-vaccinated-with-typhoid-conjugate-vaccine-in-africa/. Accessed February, 2019.

[26] WHO, Intermittent Preventive Treatment in Infants, https://www.who.int/malaria/areas/preventive_therapies/infants/en/?fbclid=IwAR1yumPwTyZEqBUzCIlPatU8pafeR9qUbNBYTA-vf8_38iyhvAumqK7xTlE. Accessed February, 2019.

[27] WHO, Intermittent Preventive Treatment during Pregnancy, https://www.who.int/malaria/areas/preventive_therapies/pregnancy/en/. Accessed February, 2019.

[28] Bill and Melinda Gates Foundation, New grants to accelerate malaria research and development, https://www.gatesfoundation.org/Media-Center/Press-Releases/2003/09/Grants-for-Malaria-Research. Accessed February 2019.

[29] Huet N & Paun C, Meet the world’s most powerful doctor: Bill Gates, Politico, 4th May 2017, https://www.politico.eu/article/bill-gates-who-most-powerful-doctor/?fbclid=IwAR1t3JJlmxNRTqcZpgvo4dPAFtrZw5vknQJRd_4gDPaU06emIgnLGUtMl6s. Accessed February, 2019.

[30] Bill and Melinda Gates Foundation, How We Work: Grant, WHO, https://www.gatesfoundation.org/How-We-Work/Quick-Links/Grants-Database/Grants/2006/10/OPP37476. Accessed February, 2019.

[31] McNeil DG, Gates Foundation’s Influence Criticized, New York Times, 16th February 2008, https://www.nytimes.com/2008/02/16/science/16malaria.html?fbclid=IwAR1otqtbJWZ8t4lO-XIVDRfQmasdDlTR5Iy6BkjoCh65fDhCECvTazjIkAI. Accessed February 2019.

[32] VCU School of Medicine, Myron Levin M’67: A pioneer of the modern discipline of vaccinology, https://wp.vcu.edu/somdiscoveries/2017/05/myron-levine-m67-a-pioneer-of-the-modern-discipline-of-vaccinology/. Accessed February, 2019.

[33] [IOM, Committee on the Perspectives on the Role of Intermittent Preventive Treatment for Malaria in Infants, 2008, available at: https://www.who.int/immunization/sage/10_IOM_report_on_IPTi.pdf. Accessed February 2019.

[34] UW Dept of Global Health, Robert Newman, https://globalhealth.washington.edu/faculty/robert-newman. Accessed February 2019.

[35] Heymann DL, Antenatal chloroquine chemoprophylaxis in Malawi: chloroquine resistance, compliance, protective efficacy and cost, Trans R Soc Trop Med Hyg,.1990;84(4):496-8.] [Kayentao K et al, Comparison of Intermittent Preventive Treatment with Chemoprophylaxis for the Prevention of Malaria during Pregnancy in Mali, The Journal of Infectious Diseases, 2005, 191(1):109–116.

 [36] Cone M, Should DDT be used to combat malaria? Scientific American, 4th May 2009, https://www.scientificamerican.com/article/ddt-use-to-combat-malaria/. Accessed February 2019.

[37] WorldWatch, Malaria, Mosquitos and DDT, http://www.worldwatch.org/node/517. Accessed February. 2019.

[38] AlJazeera, Toxic City: The cost of gold-mining in South Africa, https://www.aljazeera.com/programmes/specialseries/2019/01/toxic-city-cost-gold-mining-south-africa-190123160346656.html?ref=hvper.com. Accessed February 2019.

[39] WHO, Household air pollution and health, https://www.who.int/news-room/fact-sheets/detail/household-air-pollution-and-health. Accessed February, 2019.