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WHAT'S NEW THIS THURSDAY: NUTRITION IN THE FIRST 1000 DAYS OF LIFE; POOR QUALITY ANTIMALARIALS; IVDPV TYPE 3 IN INFANT, SOUTH AFRICA

Wednesday, 6th of June 2012

• NUTRITION IN THE FIRST 1000 DAYS OF LIFE

 

From Save The Children 

Below, statistics, key findings and recommendations from the Executive Summary. The full text is at

http://www.savethechildren.org/atf/cf/%7B9def2ebe-10ae-432c-9bd0-df91d2eba74a%7D/STATE-OF-THE-WORLDS-MOTHERS-REPORT-2012-FINAL.PDF

 

Vital Statistics 

• Malnutrition is the underlying cause of more than 2.6 million child deaths each year.

171 million children – 27 percent of all children globally – are stunted, meaning their bodies and minds have suffered permanent, irreversible damage due to malnutrition.

In developing countries, breastfed children are at least 6 times more likely to survive in the early months of life than non-breastfed children.

If all children in the developing world received adequate nutrition and feeding of solid foods with breastfeeding, stunting rates at 12 months could be cut by 20 percent.

Breastfeeding is the single most effective nutrition intervention for saving lives. If practiced optimally, it could prevent 1 million child deaths each year.

Adults who were malnourished as children can earn an estimated 20 percent less on average than those who weren’t.

The effects of malnutrition in developing countries can translate into losses in GDP of up to 2-3 percent annually.

Globally, the direct cost of malnutrition is estimated at $20 to $30 billion per year.

Key findings

 

1. Children in an alarming number of countries are not getting adequate nutrition during their first 1,000 days. Out of 73 developing countries –which together account for 95 percent of child deaths – only four score “very good” on measures of young child nutrition. Our Infant and Toddler Feeding Scorecard identifies Malawi, Madagascar, Peru and Solomon Islands as the top four countries where the majority of children under age 2 are being fed according to recommended standards. More than two thirds of the countries on the Scorecard receive grades of “fair” or “poor” on these measures overall, indicating vast numbers of children are not getting a healthy start in life. The bottom four countries on the Scorecard – Somalia, Côte d'Ivoire, Botswana and Equatorial Guinea – have staggeringly poor performance on indicators of early child feeding and have made little to no progress since 1990 in saving children’s lives. (To read more, turn to pages 26-31.)

 

2. Child malnutrition is widespread and it is limiting the future success of millions of children and their countries. Stunting, or stunted growth, occurs when children do not receive the right type of nutrients, especially in utero or during the first two years of life. Children whose bodies and minds are limited by stunting are at greater risk for disease and death, poor performance in school, and a lifetime of poverty. More than 80 countries in the developing world have child stunting rates of 20 percent or more. Thirty of these countries have what is considered to be “very high” stunting rates of 40 percent or more. While many countries are making progress in reducing child malnutrition, stunting prevalence is on the rise in at least 14 countries, most of them in sub-Saharan Africa. If current trends continue, Africa may overtake Asia as the region most heavily burdened by child malnutrition. (To read more, turn to pages 15-21.)

 

3. Economic growth is not enough to fight malnutrition. Political will and effective strategies are needed to reduce malnutrition and prevent stunting. A number of relatively poor countries are doing an admirable job of tackling this problem, while other countries with greater resources are not doing so 

Key findings

 

1. Children in an alarming number of countries are not getting adequate nutrition during their first 1,000 days. Out of 73 developing countries – which together account for 95 percent of child deaths – only four score “very good” on measures of young child nutrition. Our Infant and Toddler Feeding Scorecard identifies Malawi, Madagascar, Peru and Solomon Islands as the top four countries where the majority of children under age 2 are being fed according to recommended standards. More than two thirds of the countries on the Scorecard receive grades of “fair” or “poor” on these measures overall, indicating vast numbers of children are not getting a healthy start in life. The bottom four countries on the Scorecard – Somalia, Côte d'Ivoire, Botswana and Equatorial Guinea – have staggeringly poor performance on indicators of early child feeding and have made little to no progress since 1990 in saving children’s lives. (To read more, turn to pages 26-31.)

 

2. Child malnutrition is widespread and it is limiting the future success of millions of children and their countries. Stunting, or stunted growth, occurs when children do not receive the right type of nutrients, especially in utero or during the first two years of life. Children whose bodies and minds are limited by stunting are at greater risk for disease and death, poor performance in school, and a lifetime of poverty. More than 80 countries in the developing world have child stunting rates of 20 percent or more. Thirty of these countries have what is considered to be “very high” stunting rates of 40 percent or more. While many countries are making progress in reducing child malnutrition, stunting prevalence is on the rise in at least 14 countries, most of them in sub-Saharan Africa. If current trends continue, Africa may overtake Asia as the region most heavily burdened by child malnutrition. (To read more, turn to pages 15-21.)

 3. Economic growth is not enough to fight malnutrition. Political will and effective strategies are needed to reduce malnutrition and prevent stunting.  A number of relatively poor countries are doing an admirable job of tackling this problem, while other countries with greater resources are not doing so Community health workers and midwives meet critical needs in these communities by screening children for malnutrition, treating diarrhea, promoting breastfeeding, distributing vitamins and other micronutrients, and counseling mothers about balanced diet, hygiene and sanitation. The “lifesaving six” interventions highlighted in this report can all be delivered in remote, impoverished places by well-trained and well-equipped community health workers.

In a number of countries – including Cambodia, Malawi and Nepal – these health workers have contributed to broad-scale success in fighting malnutrition and saving lives. (To read more, turn to pages 32-37.)

 

4. We know how to save millions of children. Save the Children has highlighted six low-cost nutrition interventions with the greatest potential to save lives in children’s first 1,000 days and beyond. Universal coverage of these “lifesaving six” solutions globally could prevent more than 2 million mother and child deaths each year. The lifesaving six are: iron folate, breastfeeding, complementary feeding, vitamin A, zinc and hygiene. Nearly 1 million lives could be saved by breastfeeding alone. This entire lifesaving package can be delivered at a cost of less than $20 per child for the first 1,000 days. Tragically, more than half of the world’s children do not have access to the lifesaving six.

(To read more, turn to pages 23-26.)

 

5. Health workers are key to success. Frontline health workers have a vital role to play in promoting good nutrition in the first 1,000 days. In impoverished communities in the developing world where malnutrition is most common, doctors and hospitals are often unavailable, too far away, or too expensive.

 

6. In the industrialized world, the United States has the least favorable environment for mothers who want to breastfeed. Save the Children examined maternity leave laws, the right to nursing breaks at work, and several other indicators to create a ranking of 36 industrialized countries measuring which ones have the most – and the least – supportive policies for women who want to breastfeed. Norway tops the Breastfeeding Policy Scorecard ranking. The United States comes in last. (To read more, turn to pages 39-43.)

 

Recommendations 

1. Invest in proven, low-cost solutions to save children’s lives and prevent stunting. Malnutrition and child mortality can be fought with relatively simple and inexpensive solutions. Iron supplements strengthen children’s resistance to disease, lower women’s risk of dying in childbirth and may help prevent premature births and low birthweight. Six months of exclusive breastfeeding increases a child’s chance of survival at least six-fold. Timely and appropriate complementary feeding is the best way to prevent a lifetime of lost potential due to stunting. Vitamin A helps prevent blindness and lowers a child’s risk of death from common diseases. Zinc and good hygiene can save a child from dying of diarrhea. These solutions are not expensive, and it is a tragedy that millions of mothers and children do not get them.

 

2. Invest in health workers – especially those serving on the front lines – to reach the most vulnerable mothers and children. The world is short more than 3 million health workers of all types, and there is an acute shortage of frontlineworkers,  including community health workers, who are critical to deliveringthe nutrition  solutions that can save lives and prevent stunting. Governments and donors should work together to fill this health worker gap by recruiting, training and supporting new and existing health workers, and deploying them where they are needed most.

 

3. Help more girls go to school and stay in school. One of the most effective ways to fight child malnutrition is to focus on girls’ education. Educated women tend to have fewer, healthier and better-nourished children. Increased investments are needed to help more girls go to school and stay in school, and to encourage families and communities to value the education of girls. Both formal education and non-formal training give girls knowledge, self-confidence, practical skills and hope for a bright future. These are powerful tools that can help delay marriage and child-bearing to a time that is healthier for them and their babies.

 

4. Increase government support for proven solutions to fight malnutrition and save lives. In order to meet internationally agreed upon development goals to reduce child deaths and improve mothers’ health, lifesaving services must be increased for the women and children who need help most. All countries must make fighting malnutrition and stunting a priority. Developing countries should commit to and fund national nutrition plans that are integrated with plans for maternal and child health. Donor countries should support these goals by keeping their funding commitments to achieving the Millennium Development Goals and countries should endorse and support the Scaling Up Nutrition (SUN) movement. Resources for malnutrition programs should not come at the expense of other programs critical to the survival and well-being of children.(To read more, turn to page 45.)

 

5. Increase private sector partnerships to improve nutrition for mothers and children. Many local diets fail to meet the nutritional requirements of children 6-24 months old. The private sector can help by producing and marketing affordable fortified products. Partnerships should be established with multiple manufacturers, distributors and government ministries to increase product choice, access and affordability, improve compliance with codes and standards, and promote public education on good feeding practices and use of local foods and commercial products.

The food industry can also invest more in nutrition programs and research, contribute social marketing expertise to promote healthy behaviors such as breastfeeding, and advocate for greater government investments in nutrition.

 

6. Improve laws, policies and actions that support families and encourage breastfeeding. Governments in all countries can do more to help parents and create a supportive environment for breastfeeding. Governments and partners should adopt policies that are child-friendly and support breastfeeding mothers. Such policies would give families access to maternal and paternal leave, ensure that workplaces and public facilities offer women a suitable place to feed their babies outside of the home, and ensure working women are guaranteed breastfeeding breaks while on the job. In an increasingly urban world, a further example is that public transportation can offer special seats for breastfeeding mothers.

 

• POOR-QUALITY ANTIMALARIAL DRUGS IN SOUTHEAST ASIA AND SUB-SAHARAN AFRICA

Original Text

Gaurvika ML Nayyar BS a , Joel G Breman MD a, Paul N Newton MRCP b c, James Herrington PhD a

 

The Lancet Infectious Diseases, Volume 12, Issue 6, Pages 488 - 496, June 2012

Poor-quality antimalarial drugs lead to drug resistance and inadequate treatment, which pose an urgent threat to vulnerable populations and jeopardise progress and investments in combating malaria. Emergence of artemisinin resistance or tolerance in Plasmodium falciparum on the Thailand—Cambodia border makes protection of the effectiveness of the drug supply imperative. We reviewed published and unpublished studies reporting chemical analyses and assessments of packaging of antimalarial drugs. Of 1437 samples of drugs in five classes from seven countries in southeast Asia, 497 (35%) failed chemical analysis, 423 (46%) of 919 failed packaging analysis, and 450 (36%) of 1260 were classified as falsified. In 21 surveys of drugs from six classes from 21 countries in sub-Saharan Africa, 796 (35%) of 2297 failed chemical analysis, 28 (36%) of 77 failed packaging analysis, and 79 (20%) of 389 were classified as falsified. Data were insufficient to identify the frequency of substandard (products resulting from poor manufacturing) antimalarial drugs, and packaging analysis data were scarce. Concurrent interventions and a multifaceted approach are needed to define and eliminate criminal production, distribution, and poor manufacturing of antimalarial drugs. Empowering of national medicine regulatory authorities to protect the global drug supply is more important than ever.

3·3 billion people are at risk of malaria, which is endemic in 106 countries. Between 655 000 and 1·2 million people die every year from Plasmodium falciparum infection.1, 2 Much of this morbidity and mortality could be avoided if drugs available to patients were efficacious, high quality, and used correctly. Children in sub-Saharan Africa and southeast Asia have the highest risk of contracting and dying from malaria. The global burden of malaria has reduced in the past decade,3 and endemic countries are reliant on the long-term availability of effective antimalarial drugs to maintain this progress.4

In endemic regions, antimalarial drugs are widely distributed and self-prescribed (incorrectly and correctly) for the many febrile episodes attributed to malaria. Insufficient facilities to check the quality of antimalarial drugs, poor consumer and health-worker knowledge about these drugs, their cost, and the paucity of appropriate regulatory and punitive action makes these drugs attractive targets for counterfeiters.5, 6 Reports of poor-quality antimalarial drugs have increased in the past decade, partly because of growing awareness and concern;6—8 however, the issue may be much greater than it seems because most cases are probably unreported, reported to the wrong agencies, or kept confidential by pharmaceutical companies.6,9—10 Of the many public health consequences of poor-quality antimalarial drugs, drug resistance is a particular concern. Low concentrations of active pharmaceutical ingredient in poor-quality antimalarial drugs can result in subtherapeutic concentrations of drug in vivo, which contributes to the selection of resistant parasites.11, 12 Artemisinin derivatives are the most effective drugs against malaria, and artemisinin-based combination treatments are the recommended first-line treatments for P falciparum malaria.12, 13 Resistance or tolerance to artemisinin derivatives has been described in western Cambodia, and is characterised by slow rates of parasite clearance after treatment.14 Although a causal relation between poor-quality artemisinin derivatives and artemisinin resistance has not been confirmed, modelling analyses suggest that underdosing of patients can play an important part in the spread of resistance.15

Poor-quality antimalarial drugs are very likely to jeopardise the unprecedented progress and investments in control and elimination of malaria made in the past decade. In this Review we assess the issue of poor-quality antimalarial drugs, particularly the artemisinins, emphasise the mechanisms that determine their existence and effect in sub-Saharan Africa and southeast Asia, and describe potential interventions to combat this problem.

 

Best accessed at http://wwwnc.cdc.gov/eid/article/18/6/12-0037-f1.htm

 

Volume 18, Number 6—June 2012

Dispatch 

Article Contents

 

Nicksy Gumede  , Vongani Muthambi, and Barry D. Schoub

Author affiliations: National Institute for Communicable Diseases National Health Laboratory Service, Johannesburg, South Africa

Abstract

Patients with primary immunodeficiency are prone to persistently excrete Sabin-like virus after administration of live-attenuated oral polio vaccine and have an increased risk for vaccine-derived paralytic polio. We report a case of type 3 immunodeficiency-associated vaccine-derived poliovirus in a child in South Africa who was born with X-linked immunodeficiency syndrome.

Live-attenuated oral polio vaccine (OPV) is still the vaccine of choice for use in developing countries. However, reversion to virulence may occur during OPV replication in humans and may result in the rare cases of vaccine-associated paralytic poliomyelitis in OPV recipients and their close contacts. Two additional OPV-related problems that may affect polio eradication: long-term, persistent infection with OPV-derived viruses in persons with primary humoral immunodeficiencies (so-called immunodeficiency-associated vaccine-derived polioviruses [iVDPVs]); and circulating vaccine-derived polioviruses (VDPV) in areas with low rates of vaccine coverage (1). VDPV strains are defined as follows: 1) strains of types 1 and 3, which have <99% nt sequence identity to the capsid viral protein (VP) 1 coding region of the corresponding Sabin reference strain; and 2) VDPV strains of type 2, which have <99.4% nt sequence identity to the corresponding Sabin reference viral protein 1 (VP1) (1). Circulating VDPVs show marked sequence drift, indicating prolonged replication of the vaccine strain in susceptible human hosts and consequent acquisition of the phenotypic properties of neurovirulence and transmissibility.

Persons born with primary immunodeficiency have been found to be persistently infected with VDPV after exposure to OPV. Immunocompetent persons excrete polio vaccine viruses for up to 2–3 months (2), whereas prolonged excretion of VDPV for 6 months to >10 years has been found in persons with primary humoral immunodeficiency (3–6). The risk for vaccine-associated paralytic poliomyelitis is >3,000-fold higher for these patients (7). We report a case of type 3 iVDPV in a child in South Africa who was born with X-linked immunodeficiency syndrome.

The Patient

The patient, a 10-month-old boy, was born at term on October 28, 2010; X-linked immunodeficiency syndrome was diagnosed after he received 3 scheduled doses of polio vaccine (1 OPV dose at birth and 2 inactivated poliovirus vaccine doses at 10 and 14 weeks). On September 18, 2011, fever developed (38.5°C–40.0°C), and the next day, vomiting and 2 episodes of tonic-clonic convulsions occurred. A lumbar puncture was performed, and testing of cerebrospinal fluid (CSF) showed pleocytosis and mild increase of proteins. His condition deteriorated, and on day 5, acute flaccid paralysis developed, with generalized hypotonia and reduced power and reflexes in all limbs, more marked in the lower limbs. Respiratory distress developed, and some involvement of the facial nerve was manifested by left-sided eye drooping, mouth deviation, and drooling. A lumbar puncture was repeated on day 5, and CSF was positive by PCR for enterovirus and a pleocytosis. Stool samples taken on days 5 and 9 were positive for enterovirus, which was subsequently characterized as poliovirus type 3.

Beginning 15 days after the onset of paralysis, intravenous immunoglobulin (National Bioproducts Institute, KwaZulu-Natal, South Africa) with a titer for polio type 3 neutralizing antibodies of 4–8 IU was administered daily for 32 days, followed by alternate days to a total of 43 doses. The patient improved gradually, and strength was regained in all limbs, with the exception of residual paresis in the right lower limb. CSF became negative for poliovirus PCR 2 weeks after immunoglobulin therapy began, and stool excretion of poliovirus ceased on day 70, 55 days after initiation of immunoglobulin therapy.

Extracts of stool specimens were treated with chloroform and cultured on human rhabdomyosarcoma cell line, used for enterovirus isolation, and mouse L cells expressing the human poliovirus receptor, used specifically for poliovirus isolation (8). To distinguish whether the poliovirus isolates were of vaccine or wild origin, real-time PCR tests were performed, targeting the VP1 coding region (9). In addition, to detect mutant and recombinant poliovirus vaccine strains, a vaccine-derived, real-time screening assay was performed (David Kilpatrick, pers. comm.).

All Sabin 3 strains were sequenced at 3 regions of the genome: 5′ untranslated region, VP1, and 3D. The sequence analysis of all viruses revealed a mutation at nt 472 of the 5′ untranslated region (U₄₇₂→C), a critical attenuating mutation feature for Sabin 3. This substitution in the internal ribosomal site restores the original structure of the stem loop and permitting the initiation of translation of the poliovirus RNA template (10,11) The reversion at that site is under strong selection during replication in the human intestine and is associated with the attenuated phenotype in Sabin 3 (12). The VP1 region showed 2 reversions of the capsid determinant; C₂₄₉₃→U appear to be the main determinants of the attenuated phenotype (1), and at position 54 for alanine amino acid mutated to valine (Ala₅₄→Val) that can act as a suppressor of the temperature sensitivity and attenuated phenotype (13). At the 3D region, the sequence analysis showed no recombinant.

Both stool samples showed mixed bases at 12 positions, consistent with the presence of at least 2 main genetic variants in the virus population (Table). Isolates with mixed bases are characteristic of iVDPVs, which suggests the existence of co-replicating poliovirus lineages within immunodeficient patients (1,5).

Figure

 

Figure. . . Neighbor-joining tree of immunodeficiency-associated vaccine-derived poliovirus isolates from infant, South Africa, 2011. The tree was derived from the viral protein (VP) 1 region and rooted at the Sabin 3...

The relationships among the VP1 sequences of the 3 isolates were summarized in a tree constructed by using the neighbor-joining method (14) and rooted to the Sabin 3 sequence (Figure). The iVDVP isolates differed from the Sabin 3 OPV strain at 1.1% and from each other by 1.4% at a VP1 region, similar to the rate of nucleotide sequence evolution in poliovirus as described by Jorba et al. (15). The chronic iVDPV infection could have been initiated by the birth dose. The shallow branches correspond to 2 lineages (A, CSF, and B, stool). The extensive divergence of the two lineages was not surprising as the viruses originated from 2 sources (CSF and stool samples) taken 4 days apart. The VP1 sequence of lineage B was ambiguous at several positions, which suggests the virus population was of mixed variants. All sequences determined in this study were derived from Sabin 3 strain.

Conclusions

Cases of iVDPV are rare; especially rare is type 3. Only ≈50 cases had been reported in the literature as of March 2011 and, to our knowledge, none in sub-Saharan Africa. We characterized 2 separate lineages of type 3 poliovirus in this patient, demonstrating separate evolution of the virus. A relatively rapid clinical and virologic response to intravenous immunoglobulin averted chronic excretion of the virus. Persistent excretion of VDPV in primary immunodeficient patients remains a potential risk to the global eradication of polio, as long as OPV is still used.

Ms Gumede is a medical scientist pursuing a PhD at the University of Pretoria, South Africa. Her research interests include disease epidemiology, clinical research, and polioviruses.

Acknowledgment

We thank the National Institute for Communicable Diseases Polio Working Group for excellent technical assistance and M. Kriel for clinical information.

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