Monday, January 4, 2010

Individual Project

A review of the relationship between malnutrition and disease, specifically HIV and malaria, in countries of sub-Saharan Africa and implications for Mozambique

Malnutrition is highly prevalent in developing countries and is considered to be the underlying cause of more than 50% of all childhood deaths in the world. In sub-Saharan Africa, 38% of children under the age of five years suffer from chronic malnutrition or stunting, while acute malnutrition or wasting affects 9% of preschool children (Fillol et al). Some subsequent diseases of malnutrition are kwashiorkor and marasmus. Kwashiorkor is a specific “wasting away” disease caused by protein deficiency in third world countries. Symptoms include apathy, muscular wasting, and edema of mainly the abdominal region. This disease may be a result of sudden inadequate food supplies in the family due to another birth or trauma. Marasmus is a disease resulting from a lack of both sufficient calories and protein in the diet. Symptoms include fretfulness and emaciation, as this disease is more chronic than kwashiorkor (“Nutrient”). Malnutrition is a significant public health problem in the sub-Saharan region, and is a strong risk factor for admission to hospital and death. In Mozambique, 41% of children under the age of five suffer from chronic malnutrition, otherwise known as “stunting.” 23% of children in the same age group are underweight, and 4% suffer from acute malnutrition, known as “wasting” (The World Bank).

Unfortunately, the same developing countries plagued by malnutrition also suffer from malaria and HIV endemics. Children and adults living in malaria-endemic areas often have a high prevalence of malnutrition and deficiencies of micronutrients such as vitamin A, folate, and zinc. Malaria is the most common reason for hospitalization among children and is a leading contributor to anemia. By the year 2000, there were more than 100 million malaria episodes among children in sub-Saharan Africa. Approximately 800,000 children die from malaria in this region every year (SanJoaquin et al). In Mozambique, malaria is responsible for 40% of all outpatients and up to 60% of pediatric inpatients hospitalized. This disease is the major cause of mortality in hospitals, accounting for 30% of all deaths. In some areas, 90% of children under five years old are infected with malaria parasites (“Malaria”). In the overall population of Mozambique, malaria accounts for approximately 9% of all deaths (“…Country”). However, malaria is a preventable and treatable disease if measures are taken in a timely manner.

At the end of 2008, an estimated 22.4 million adults and children were living with HIV (Human Immunodeficiency Virus) in sub-Saharan Africa. During that same year, around 1.4 million Africans died from AIDS. It is thought that 14.1 million African children have lost one or both parents to this epidemic (“Sub”). Sub-Saharan Africa accounts for around 90% of the children orphaned by AIDS. Mother-to-child transmission of HIV occurs in 30%-45% of cases in the region. Sub-Saharan Africa is home to more than 66% (about 25 million) of the world’s total number of HIV/AIDS cases, with 80% of affected women worldwide living in this region (Fawzi et al). In Mozambique HIV/AIDS is the number one overall cause of death in the country (28%), with an estimated 12.5% of adults (ages 15-49) infected (“…Country”). Poor nutrition and HIV disease progression have been thought to propagate the vicious cycle that further deteriorates patients’ health and ultimately leads to mortality. Severe malnutrition in childhood associated with HIV infection poses a very serious public health challenge. Specifically, HIV infection, malaria, and diarrheal diseases have been shown to adversely affect growth and are associated with deficiencies in vitamin A (Villamor et al). Recent peer-reviewed research associates nutritional supplementation with increased efficiency in prevention and treatment of malaria and HIV, as discussed below.

In the study Impact of child malnutrition on the specific anti-Plasmodium falciparum antibody response, researchers investigated the relationship between malaria, malnutrition, and specific immunity. It has been recognized that malnutrition compromises the immune function, resulting in higher risk of infection (Fillol et al). During the rainy season (early July to October), rural Senegalese preschool children were initially divided into subcategories of malnutrition and followed during the course of one malaria season. Malnutrition was defined as stunting or wasting based on height-for-age and weight-for-height ratios. Baseline measurements were taken initially, and followed by final assessments at the end of the malaria season. Parasite densities were estimated in thick blood films with a set standard of white-blood-cell counts. Weight and recumbent length measurements were taken via appropriate measures based on the age of subjects.

The anti-Plasmodium falciparum IgG antibody (Ab) was then evaluated as directed to total antigens assessed. Finally, generalized linear regressions were used to estimate the association between IgG Ab levels and malnutrition adjusted for intensity of infection and groups of age. Results showed that “both the prevalence of anti-malarial immune responders and specific IgG Ab levels were significantly lower in malnourished children than in controls,” (Fillol et al). Stunted and severely stunted children showed a significant difference in down-regulation of the specific Ab response. However, all responses seemed to be independent of the intensity of the infection. The authors concluded that child malnutrition, especially stunting, may down-regulate the anti-P. falciparum Ab response. The results act as evidence for the influence of nutritional status on specific anti-malarial immune response. Further, the authors claim that this implies a need to take child malnutrition into account during vaccine trials and epidemiological studies.

The effectiveness of anti-malarial drug treatments in relation to malnourishment is studied in the article, Reduced Efficacy of Intermittent Preventive Treatment of Malaria in Malnourished Children. Presently, intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) has been shown to reduce malaria episodes by 20 to 59% across Africa (Danquah et al). However, the large number of cases of malnutrition in African infants may affect the protective effect of this drug treatment. A cohort of 1,200 infants in northern Ghana received doses of IPTi after baseline measurements were taken and nutritional status evaluated. Over the course of 21 months, infants were taken to routine checkups where weight length/height were measured and related to age and sex. The nutritional state was then determined at the age of one year and at each IPTi administration. Results showed that the protective effects of IPTi were almost halved in malnourished infants with regards to malaria. In fact, malnourished infants receiving SP were found to experience an excess of malaria episodes (Danquah et al). The authors concluded that nutritional status influences the effect of this drug treatment. In addition, IPTi did not improve the growth of infants who were malnourished, as opposed to their nutritionally stable counterparts. Insufficient folate intake and subsequent deficiency was thought to complicate overall malnutrition and partially lead to results observed. The authors also concluded that the administration of SP in malnourished and folate-deficient children eventually may contribute to the development of severe anemia.

Vitamin A and zinc are known to be essential for normal immune function, and are may help reduce the risk of malaria infection (Zeba et al). This topic is investigated in the study, Major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children in Burkina Faso: a randomized double blind trial. Subjects were children from a rural village in Burkina Faso who received supplements of vitamin A and zinc for a period of six months. The village has a government health center where the children were examined. History of fever, immunization data, physical examination, height and weight were all recorded for clinical and anthropometric data. Blood samples for hematology analysis and malaria parasite detection were also taken. At the end of the study, the prevalence of malaria was significantly lower in the supplemented group (34% versus 3.5% respectively, p<0.001). The mean parasite density was higher in the placebo group compared to the supplemented group at the end of the study (p=0.048) (Zeba et al). However, the authors observed that wasting and stunting with regards to nutritional status continued to be severed in both the treated and placebo group. The authors concluded that these results suggest that combined supplementation of vitamin A and zinc may effectively reduce malaria-associated morbidity and could be a segment of malaria control strategies in African children.

In sub-Saharan Africa, HIV infection and malaria are highly prevalent. When these diseases interact with poor nutritional status, they account for a large proportion of deaths in children and infants (Villamor et al). Vitamin A Supplements Ameliorate the Adverse Effect of HIV-1, Malaria, and Diarrheal Infections on Child Growth examines the effect of vitamin A supplements on the growth of participating Tanzanian children. Results showed that malaria (P. falciparum) and HIV infection were found in 24% and 9% of the children, respectively (Villamor et al). Supplementation with vitamin A among children who were infected with HIV resulted in significant length increase and a higher yearly weight gain. Also, the risk of stunting associated with acute, persistent diarrhea was relatively eliminated by vitamin A supplements. The authors concluded that vitamin A supplementation improves linear and ponderal growth in infants who are infected with HIV and malaria, respectively, and decreases the risk of stunting associated with persistent diarrhea.

Integrated care may be necessary when implementing public health policies, due to the association of HIV infection with severe malnutrition in childhood. This is addressed in the study, HIV prevalence in severely malnourished children admitted to nutrition rehabilitation units in Malawi: Geographical & seasonal variations a cross-sectional study. In Nutrition Rehabilitation Units, HIV infection directly affects all of the principle treatment outcomes and must be taken into account when assessing individual performance of a site. Surveys were done over a period of two weeks during both the post harvest/dry season (June) and rainy/hungry season (February). A differentiation was also made between northern, central, and southern regions of Malawi. Results showed that seasonal and geographical HIV prevalence variations were marked and were statistically significant (Thurstans et al). HIV prevalence was significantly higher in the southern region of Malawi (36.9%), in urban areas (32.9%), and during the dry/post-harvest season. The authors concluded that Nutrition Rehabilitation Units could act as “entry points to HIV treatment and support [programs] for affected children and families,” (Thurstans et al).

Studies have also been done regarding the effect of supplementation on HIV in sub-Saharan African adults. Both children and adults were reviewed in the article, Studies of Vitamins and Minerals and HIV Transmission and Disease Progression. Among children, periodic supplementation with vitamin A starting at six months of age has been shown to be beneficial in reducing mortality and morbidity among both HIV-infected and uninfected children (Fawzi et al). Daily multivitamin supplements were found to reduce HIV disease progression among me and women, and thus may provide a type of low-cost intervention for adults in the early stages of HIV disease. This would prolong the time before antiretroviral therapy is recommended. Studies reviewed included those located in Malawi, South Africa, and Tanzania. The authors concluded that, “Multivitamin supplementation has been shown to reduce clinical HIV disease progression in several well-designed observational studies and randomized trials,” (Fawzi et al).

When treating HIV-infected patients, it is essential to take into account nutritional status and overall health. This topic was addressed in the research article Predictors of mortality in HIV-infected patients starting antiretroviral therapy in a rural hospital in Tanzania. The aim of this study was to assess mortality and to identify predictors of mortality in HIV-infected adult patients starting antiretroviral treatment in a rural Tanzanian hospital (Johannessen et al). Baseline data was collected and the main endpoint of the study was considered as death from all causes. Results showed that predictors of mortality were severed and moderate anemia, thrombocytopenia and severe malnutrition (Johannessen et al). Mortality was also found to increase with decreasing hemoglobin and Body Mass Index (BMI). Results also showed that estimated one year mortality was nearly 50% among patients with severe malnutrition. Severe anemia observed can be applied to the concept of using hemoglobin levels to identify HIV-infected patients with poor prognosis, as concluded by the authors.

Challenges in the treatment of both malaria and HIV revolve around the lack of resources; human, nutritional, and technical. Programs in many sub-Saharan African countries, including Mozambique, have been implemented as an endeavor to combat these growing epidemics. According to the World Health Organization, obstacles in Mozambique to overcome when addressing the malaria endemic are: shortage of human resources, weak supervision of implementation of activities, need of training for malaria health care workers, need for adequate storage and distribution of therapy materials and tests, and the existence of a weak monitoring and evaluation system (“Malaria”). However, improvements have been made in the country regarding malaria prevention and treatment. These include adoption of the Intermittent Preventive treatment (IPT) strategy for pregnant women, introduction of first-line treatment at the community level, nationwide production and distribution of educational materials for community health workers, as well as the introduction for rapid diagnostic tests for malaria diagnosis (“Malaria”). The prevention and treatment of HIV/AIDS has also been addressed by both domestic and foreign programs in Mozambique. Financial and human resources are made available by institutions such as the National Center for HIV/AIDS, the Ministry of Health, the Center for Disease Control, and many more.

While malaria and HIV remain urgent public health issues, there is hope that with proper prevention and treatment, the progress of these epidemics will be hindered. In relation to malnutrition, micronutrient supplementation may prove to be a cheap, effective, and accessible route to improving the mortality rates associated with malaria and HIV in sub-Saharan Africa.

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Works Referenced

Danquah, Ina, et al. Reduced Efficacy of Intermittent Preventive Treatment of Malaria in Malnourished Children. Antimicrobial Agents and Chemotherapy 2009 May; 53(5): 1753-1759

Fawzi, Wafaie, et al. Studies of Vitamins and Minerals and HIV Transmission and Disease Progression. Journal of Nutrition 2005 Apr; 135(4): 938-44

Fillol, Florie, et al. Impact of child malnutrition on the specific anti-Plasmodium falciparum antibody response. Malaria Journal 2009; 8(116)

Johannessen, Asgeir, et al. Predictors of mortality in HIV-infected patients starting antiretroviral therapy in a rural hospital in Tanzania. BMC Infectious Diseases 2008 Apr; 8(52)

“Malaria in Mozambique.” World Health Organization. 31 Dec 2009. http://www.who.int/countries/moz/areas/malaria/en/index.html

“Mozambique: Country Health System Fact Sheet 2006.” World Health Organization. 31 Dec 2009. http://www.afro.who.int/home/countries/fact_sheets/mozambique.pdf

“Mozambique and the Global Fund.” The Global Fund. 31 Dec 2009. http://www.theglobalfund.org/programs/countrystats/?lang=en&countryID=MOZ

“Mozambique: National Statistics.” The World Bank. 31 Dec 2009. http://web.worldbank.org/WBSITE/EXTERNAL/COUNTRIES/AFRICAEXT/MOZAMBIQUEEXTN/0,,contentMDK:20585276~pagePK:141137~piPK:141127~theSitePK:382131,00.html

“Mozambique: Statistics.” UNICEF. 31 Dec 2009. http://www.unicef.org/infobycountry/mozambique_statistics.html

“Nutrient Deficiency Diseases.” 31 Dec 2009. http://science.jrank.org/pages/4796/Nutrient-Deficiency-Diseases-Marasmus-kwashiorkor.html

“Sub Saharan Africa: HIV and AIDS Statistics.” AVERT. 31 Dec 2009. http://www.avert.org/subaadults.htm

Thurstans, Susan, et al. HIV prevalence in severely malnourished children admitted to nutrition rehabilitation units in Malawi: Geographical & seasonal variations a cross-sectional study. BMC Pediatrics 2008; 8(22)

Villamor, Eduardo, et al. Vitamin A Supplements Ameliorate the Adverse Effect of HIV-1 Malaria, and Diarrheal Infections on Child Growth. BMC Pediatrics 2002 Jan; 109(1)

Zeba, Augustin N, et al. Major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children in Burkina Faso: a randomized double blind trial. Nutrition Journal 2008; 7(7)

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