Homeopathy for HIV/AIDS in resource limited settings in Swaziland
by Barbara Braun
INTRODUCTION
Swaziland is a small country situated between South Africa and Mozambique in southern Africa. Since the first cases of AIDS were reported in 1986 there has been an exponential increase in infection, and it is now estimated to have the highest prevalence in the world. Women have been particularly affected by the epidemic with a prevalence of 31% in women aged between 15 – 49. The HIV/AIDS epidemic has had huge repercussions, orphans and vulnerable children account for an estimated 15% of the total population (1) and the life expectancy is now estimated at 45 years, one of the lowest in the world.
These statistics are set against a backdrop of existing poverty, a patriarchal society with a history of polygamy combined with a series of droughts resulting in many people being vulnerable to the adverse effects of disease. Lack of adequate food leaves people less able to cope with HIV, as effective treatment depends on a good diet.
The deaths of many adults have resulted in a youthful population with approximately 39% of the population under the age of 14, and those over 65 accounting for 3.7%. Many children are left orphaned or in the care of grandparents, or in some cases left to fend for themselves in child-headed households.
Stigma associated with HIV and AIDS prevents many Swazis from being tested or declaring their status if they are positive. The government estimates that only 16% of people aged 15 – 49 have been tested for HIV and know their status. Swazi traditional opinion links AIDS with sexual promiscuity and often causes HIV-positive people to be rejected by their families. The National Emergency Response for HIV and AIDS (NERCHA) has launched a series of behaviour change campaigns, but this has to be viewed as a long-term issue. As a result of traditions such as polygamy, young women marry older men with whom they are not able to insist on condom use, and in a patriarchal society these women are especially vulnerable to sexually transmitted disease.
In 2003 the government launched its strategy to provide free nationwide antiretroviral treatment (ART). By the end of 2009 ART had become available at 89 health facilities across the country and just over 47 000 people were receiving ART. Swaziland‘s HIV/AIDS health policy states that once a person has been tested positive, their CD4 count is monitored by the Voluntary Counselling and Testing centres (VCT) at various health centres around the country.
If a CD4 count drops below 350, a person is given anti retroviral drugs free of charge.
If a person is raped, they are given anti retroviral drugs free of charge as a preventative measure.
If a pregnant mother is HIV positive, within 72 hours of birth, the mother and child are given Nevirapine to prevent mother to child transmission. This is also given free of charge.
Despite the success of the ART programme and the high level of funding for HIV treatment, limited infrastructure and human resources hinder the delivery of effective treatment and care. Around 80% of the population lives within 8 kilometres of a facility that provides at least antenatal care and access for rural communities is limited. There are only 2 physicians available for every 10 000 people and one nurse for every 356 people.
ANTIRETROVIRAL TREATMENT (ART)
There is no documented cure for infection caused by the human immunodeficiency virus (HIV) but a number of drugs slow or halt the disease progression. Drugs for HIV infection increase life expectancy considerably especially if patients have access to a healthy lifestyle and sufficient food. While most individuals tolerate ART well, some may suffer side effects.
Severe side effects are common requiring one out of six patients to change ART because of toxicity. Some patients choose to discontinue ART rather than endure debilitating side effects. Interruptions in ART dosing can quickly result in drug resistance. Drug resistance to first line ART is a known complication occurring within five years. In Africa 22% of people living with HIV/AIDS treated with first line ART become drug resistant and new and second line drugs are not always available.
The medical scientific community is obliged to explore other avenues to seek solutions, which may be more acceptable and appropriate in varied treatment settings in the developing world.
The principles of ART are aimed at reducing the plasma viral load as much as possible and for as long as possible. It should be started before the immune system is irreversibly damaged, however the need for early drug treatment should be balanced against the risk of toxicity. In addition commitment to treatment and strict adherence over many years is required. Once started, antiretroviral treatment must be taken every day for life. Every missed dose increases the risk of developing resistance. It is therefore vital that people receiving antiretroviral treatment get all the help they need to minimise the impact of side effects. There are several ways to lessen the harm, either by treating the side effects or by switching to alternative antiretroviral drugs.
Common toxicity side effects seen with the use of ART.
Side effects vary from person to person and it is impossible to predict exactly how each individual will be affected. Some people take antiretroviral treatment for years with few problems, while others find the same drugs intolerable. Nevertheless some characteristics and pre-existing conditions (such as high blood pressure or hepatitis infection) are known to increase the risk of certain side effects.
Some side effects appear shortly after starting an antiretroviral drug and disappear within a few weeks as the body gets used to the new chemicals. This is often the case with nausea, diarrhoea and headache, for example.
Unfortunately other side effects – such as peripheral neuropathy (nerve damage) and lipodystrophy (fat redistribution) – tend to worsen over time and may never go away. Also some problems may not emerge until months or even years, after treatment is started.
Most side effects are not uniquely associated with a particular drug, and sometimes it can be difficult to identify the cause. HIV infection itself is capable of producing many of the symptoms that also occur as drug side effects. Other possible causes include opportunistic infections, stress, diet, and non-HIV drugs. The advantage of homeopathic treatment is that it can address the symptoms regardless of the cause and can be particularly helpful in the mental and emotional sphere.
Diarrhoea is a common side effect of many antiretroviral drugs – especially protease inhibitors. Other possible causes include HIV and other infections and antibiotics. Sometimes an antiretroviral drug causes diarrhoea for only the first few weeks; in other cases this side effect lasts for as long as the drug is taken. The severity of diarrhoea also varies. While even occasional attacks may be inconvenient and embarrassing, persistent diarrhoea can also lead to dehydration, poor absorption of nutrients and drugs, weight loss and fatigue. Almost all antiretroviral drugs, as well as many other medications, can cause nausea and vomiting, especially during the first few weeks of treatment. If nausea and vomiting are severe, or occur with other symptoms such as dizziness, thirst, fever, muscle pain, diarrhoea, headache or jaundice, then this may indicate a more serious problem such as lactic acidiosis or pancreatitis.
Rashes often appear as a side effect of antiretroviral treatment. These may be itchy but are usually harmless and short-lived. However, severe rashes and severe hypersensitivity including Stevens Johhson syndrome can occur with Nevirapine, and more rarely with some other drugs.
Lipodystrophy involves losing or gaining body fat, often in ways that can be disfiguring and stigmatising. Three main patterns are seen:
Losing fat on the face, arms, legs and buttocks, resulting in sunken cheeks, prominent veins on the limbs, and shrunken buttocks.
Gaining fat deep within the abdomen, between the shoulder blades, or on the breasts.
A mixture of fat gain and fat loss.
Although lipodystrophy sometimes affects people with HIV who have not taken any antiretroviral drugs, it occurs more often among those receiving treatment. The condition is among the most common long-term side effects of combinations of drugs from the Nuclease reverse transcriptase inhibitors (NRTI) and protease inhibitor classes. It is particularly associated with stavudine, and to a lesser extent zidovudine. The precise causes of lipodystrophy remain unknown.
Lipid abnormalities are another common side effect of some antiretroviral drugs – particularly protease inhibitors – and are often seen in people who also have lipodystrophy. Abnormal lipid levels can be harmful to health. HIV positive people taking antiretroviral treatment commonly have high levels of LDL cholesterol, low levels of HDL cholesterol, and high levels of triglyceride in the blood. Among HIV negative people such lipid abnormalities have been linked to greater risks of heart disease, stroke and diabetes.
In Swaziland, the most commonly used ART include the following, Zidovudine/Azidothymidine (AZT), Stavudine (D4T), Lamivudine (3TC), (Nevirapine) NVP, Efavirenz and Tenofovir disoproxil.
The symptoms of toxicity may include any of the following:
Appetite loss, anorexia, central nervous system effects such as vertigo, mood changes, depression, anxiety and paranoia. Fatigue, weakness, insomnia, insulin resistance and diabetes, nausea, vomiting, abdominal pain, tiredness, abnormal heart beat, and weight loss. Other symptoms seen are peripheral neuropathy with numbness and “pins and needles” and burning in the extremities and a variety of skin conditions including rashes, itching and eruptions. Headache and general body aches are also common.
It is to be noted that many of these symptoms are also to be seen in people not taking ART. In the treatment of HIV/AIDs patients already receiving ART with homeopathy the focus is on each patient and their individual picture of disease rather than the individual symptoms of side effects.
HOMEOPATHIC TREATMENT
Homeopathy provides a complementary approach to the treatment for HIV/AIDS patients. It is cost effective, accessible, easy to administer and without serious side effects or drug resistance. Homeopathic remedies cost cents per dose and do not require complex dosing regimens. Instead of introducing chemically toxic agents meant to inhibit the virus replication (but which at the same time may promote its mutation if not taken according to a precise regimen), homeopathy enhances the patient’s immune system’s ability to overcome the virus naturally. As HIV/AIDS is a disease affecting the immune response, homoeopathy, as a holistic treatment, is uniquely suited to the treatment of HIV/AIDS.
It has been observed in Botswana at the Maun Homeopathy Project, at similar Homeopathy Project clinics in Tanzania, Malawi and Kenya and in the patients treated by the Swaziland Homeopathic Project, that significant numbers of the patients on ART and Homeopathic treatment show an improvement in their health.
Homeopathic treatment given along with the ART has been seen to reduce the side effects of the toxicity and this helps patients to continue to adhere to the ART treatment regimen. Homeopathy also involves treating each case as an individual with a “tailor made” prescription for each patient. Evidence to date for this integrated approach to the treatment of HIV/AIDS has been anecdotal and therefore sound properly conducted research is essential in order to substantiate the data. The Swaziland Homeopathy Project is now able to provide a large amount of valuable information and statistical evidence of the effectiveness of homeopathic treatment from its data base.
SWAZILAND HOMOEOPATHY PROJECT (SHP) BACKGROUND
This Swaziland registered Charity was started in 2008 in response to a call to assist with the welfare of rural women working on handcraft initiatives that serve to empower rural women.
This initial impetus for homoeopathy in the rural areas of Swaziland came from Tintsaba, a women‘s weaving handcraft project, in response to the need for additional support for the women on this project and their children, particularly those who are HIV positive, regardless of whether they are on ART or not. There are many weavers in this group of 900 women — often the sole wage earners in their families — who are dying despite the conventional treatment available in the main centres. The cost of bus fares is prohibitive for many people, thus putting testing and treatment for HIV beyond the reach of many people living in remote rural areas. The women from Gone Rural, a similar initiative, (a group of about 700) are in a similar predicament and on average each has eight dependants. This has obvious repercussions for both the community and the projects themselves.
In order to justify further funding for this charity, the project set up a comprehensive database to establish the effectiveness of homoeopathic treatment. Patient and practitioners score overall health and individual symptoms at each consultation, and patient details are recorded for age, status, sex etc.
The demographics from the Swaziland Homeopathy project database indicate the following:
April 2012 from a sample of 2,200 patients
18 % tested HIV positive
40% tested HIV negative
42% are untested
Out of 1,283 patients who have been tested, 31% have tested HIV positive.
STATISTSICAL ANALYSIS OF DATA BASE RESULTS
1. Demographics:
Data from patient records of 390 patients all tested HIV positive was analysed for the period from June 2008 to April 2012.
Subgroup gender and age demographics. (April 2012)
Total Patients 390
Gender: Male 42
Female 348
Patients HIV positive only (not on ART) 192
Male 17
Female 175
Patients HIV positive receiving ART 198
Male 25
Female 173
Age groupings
Under 10: 3 10 to 19: 5 20 to 29: 44 30 to 39: 136 40 to 49: 107 50 to 59: 68 60 to 69: 22 70 to 79: 5
2. Evaluation Parameters - End Points
The end points are changes in the Practitioner and Patient overall scores, a scoring system based on the Karnofsky functional status scores, on a scale of 10, and the Practitioner Evaluated Symptom Evaluation Scale (VAS) (Appendix 2 - 4 ).
The scoring system is on a scale of 1 - 10, 10 representing full health, and is translated into the local language (siSwati). Patients are guided by the translators/clinical assistants in the interpretation of the score as a means of determining a baseline at the first consultation. From this initial score, patients can then determine at the follow-up treatments whether they have improved, stayed the same or worsened. This change can then be measured. The patient scores are obtained by translators/clinic assistants to the homoeopaths, and not by the prescribing homoeopath, to avoid bias. The prescribing homoeopath makes an independent assessment of this overall score.
The symptoms are scored by the homoeopath taking the case on a scale of 0 to 5, 5 being of the most severe degree, 0 representing the symptom having cleared.
3. Homoeopathic treatment and repertorisation. Patients are generally seen in rural mobile outreach clinics on a monthly basis. Due to the lack of electricity at most locations, cases are handwritten and repertorised manually and remedies are dispensed for a period of five weeks. Follow-up consultations are then made on a monthly basis, and prescriptions are changed accordingly. Miasmatic, constitutional and organ-specific remedies are all prescribed accordingly in a variety of potencies. The homoeopaths on these clinics prescribe using either classical homoeopathy or the layers method (Eizayaga). Due to the remote nature of many of the clinics and the lack of communication with patients in between consultations, in the severe cases both acute and chronic prescriptions are given to the patients to take in sequence on a weekly basis.
4. Homoeopathic remedies: Remedy boxes containing approximately 300 remedies are transported to the clinics, and individual prescriptions are dispensed in tablet form in small plastic envelopes with detailed instructions on how to take them. Patients are also given a handout explaining the action of homoeopathy and the importance of follow-up consultations even if they are feeling completely better. In cases of malnutrition and severe weakness, a combination of all twelve Schussler tissue salts may also be prescribed.
5. Data collection and patient confidentiality: All case details are completed on a written form, filed in individual plastic sleeves, and then entered onto the database on a weekly basis. Patient files are confidential and disclosure to third parties is prohibited.
6. Data analysis: This is carried out using the Student t test, a standard statistical analysis.
RESULTS
1. OVERALL PATIENT AND PRACTITIONER SCORES
This graph shows the average overall scores given by both the patients and the practitioners. There is not a big variation between the two and the trend shows that there is an overall improvement. (data from April 2012)
PERCENTAGE IMPROVEMENT AFTER FIRST FOLLOW-UP:
(Statistics from April 2012 database information)
This chart shows the overall average scores after the first follow up treatment.
New symptoms relate to the patients who showed a drop in their overall score which may indicate a “healing crisis” or temporary worsening of symptoms, or new symptoms in the case.
STATISTICAL ANALYSIS USING STUDENT T-TEST
SYMPTOM SCORE ANALYSIS
The number of individual (VAS) scored symptoms that appeared more than ten times was collated. These are shown below with their frequency. They reflect the overall prevalence of particular symptoms. In a HIV/AIDS group of patients with a high incidence of tuberculosis, it is not surprising that cough is the most common symptom reported.
This table illustrates data base information from August 2011
Most Frequently Reported symptoms
(more than 10 times)
Symptom No. of times reported
Cough total 178
Cough, general 90
Cough – Dry 49
Coughing with yellow sputum 26
Coughing with White sputum 13
Skin total 137
Skin eruptions 75
Skin itchy 62
Headaches total 115
Headaches general 89
Headaches, left side 15
Headache, right side 11
Grief 91
Chest total 91
Chest pain 62
Chest general 14
Asthma, general 15
Back pain 85
Numbness 51
Symptom No. of times reported
Loss of appetite 49
Over responsibility 38
Weakness 37
Herpes 32
Influenza 32
Tuberculosis 31
STI 31
Diarrhoea 31
Vertigo 28
Feet burning 25
Heartburn 20
Hot flashes 19
Vagina, itching 17
Vaginal discharge 17
Sleeplessness 14
Joint pains 14
Stomach burning 14
Mentals 13
Abscesses 13
Knee pain 13
Urine - Burning 13
Haemhorrhoids 12
Menses 12
Vomiting 12
Money worries 12
Eyes - pains 11
Uterus pain 11
Emaciation 11
COMPARISON OF MENTAL AND PHYSICAL SYMPTOMS
– CHANGE IN VAS SCORES FOR THE FIRST FOLLOW UP.
Mental symptoms clear more quickly than physical symptoms and many of the mental symptoms have cleared completely by the fourth treatment.
CHANGE IN VAS SCORES OVER TIME
This graph illustrates the improvement in symptoms over the first 6 consultations and shows that the largest improvement occurs in the first consultation.
REMEDY EFFICACY
This chart illustrates the remedies that are associated with symptom score improvement. It gives an idea of the “genus epidemicus”of the cases seen in Swaziland. The large allocation to liver drainage is due to the prescription of a drainage combination including Carduus marianus, Chelidonium, and Hydrastis Canadiensis, in low potency to assist with the detoxification of the liver in patients suffering from side effects of the ART.
ILLUSTRATIVE CASE STUDIES
The majority of our HIV/AIDS patients are women as the project works in conjunction with rural handcraft projects. However the following cases have been chosen to illustrate some of the different situations encountered in treating HIV/AIDS in Swaziland.
Case 1 - Orphaned
A large number of children are orphaned and ill from birth. This boy of 9 years is currently living with his uncle and is being abused. Both his parents have died from AIDS. His grandmother brought him to the clinic. Age 9 Orphaned
February 2012 May 2012
First consultation February 2012 - Presenting Symptoms:
Ailments from abuse (symptom score 5), Herpes, multiple open skin lesions and rash (5), diarrhoea – malnutrition (5), Dreams - nightmares, ghosts, heights, falling
First Follow up 3 May 2012
Mentals (1) Herpes (0), other skin lesions (3) Diarrhoea (0) nightmares (0)
Remedy:
Thuja occidentalis
First 30 C daily, then 200 C daily
The patient was also given a combination of all the Schussler tissue salts to improve his overall nutrition. Unfortunately one of the exciting causes in this case is the abuse and maltreatment he is receiving in his home environment and as long as this continues, homeopathic treatment can only offer a partial solution to his health.
Case 2: ART treatment failure:
A number of people are unable to tolerate the ART and despite changes in the drug regime these patients die from progressive liver and kidney damage and general organ failure.
If homeopathic remedies are given at the start of the ART regime these patients are more able to deal with the side effects and are thus able to adhere more easily and stay for longer periods on the initial treatment combination.
Adult male Age 40 years:
ART since May 2010, no infections or other apparent symptoms at start of ART, but CD4 was 189 and ART was initiated. By January 2012 CD4 had dropped to 8.
Patient first seen for homoeopathic consultation October 2011
Home visit
Presenting Symptoms : Renal failure, extreme thirst, fever, weakness, anaemia. Score 2/10
Remedies, Ph-Ac, Causticum, Kali – c : March 2012 patient passed away.
Case 3 – ART and Tuberculosis:
From the SHP database it appears that the predominant opportunistic infection of the HIV/AIDS patients encountered is Tuberculosis. This concurs with the assessment made by Medicines San Frontier in their Tuberculosis program in Swaziland. Many patients here have acquired Multiple Drug Resistant Tuberculosis and have gone through endless regimes of debilitating antibiotic treatment.
Female -Age 57
MDR TB/ART
At first consultation in 2009 (Patient receiving TB meds only)
CD4 205 (Oct 2008)
ART Initiated Feb 2010
Main Symptoms: Chronic TB infection, chronic cough, candida, weakness, emaciation, skin rash, intermittent diarrhea.
Remedies: (These were given over the period from 2008 to 2012)
Staphysagria, Phosphorus, Tuberculinum, Kali carbonicum.
This patient is a good example of how an integrated approach to the treatment of HIV/AIDs and Multiple Drug Resistant Tuberculosis may be used. A combination of conventional treatment and homeopathic remedies was very successful in this case.
Case 4. Homeopathy only
Many people are untested in Swaziland and often unwilling to do so. As the ART is only usually initiated when the CD4 is below 350 many of the patients seen are not on ART and as a result they receive Homeopathy as the predominant treatment for their presenting symptoms.
Female - Age 40
At first consultation November 2008 patient very ill but not tested.
Patient tested HIV positive in February 2010
CD4 – about 300. No ART to date.
Main Symptoms: Anxiety, chronic diarrhoea, weight loss, appetite loss, herpes, skin rash.
Remedies: (2008 to 2012)
Arsenicum album
Aurum metallicum
Rhus toxicodendron
This patient is now strong and has continued to maintain her weight and has been symptom free for long periods. She is also now able to be more productive and therefore more able to support her family with the handcraft work.
Case 5: Sexually transmitted infections
The other common infections that are associated with HIV/AIDS include other sexually transmitted infections such as gonorrhea and syphilis. These are usually treated allopathically with multiple antibiotic regimes and in HIV/AIDS patients often with little long term success as the infections keep recurring. Homeopathy can have good results in these cases.
Male - Age 56 Multiple STI
(Antibiotics no ART)
First Consult 1/2011
CD 4 (unknown)
Symptoms:
Multiple ST infections, penile chancres, extensive eruptions on external genitalia, perineum, anus, skin rash, weight loss, appetite loss, “needle pains everywhere”
Remedies:
Silicea, Nitric Acidicum,
Syphilinum, Medorrhinum
CONCLUSION:
Treating HIV and Aids with homeopathy is still about treating the totality of symptoms that the individual presents.
The Swaziland Homeopathy project data shows how the use of a simple scoring system and a comprehensive database can provide a large amount of useful ongoing clinical information. It is clear from the analysis of the information presented that homoeopathy can be a successful approach to the treatment of all HIV/AIDS patients, regardless of whether they are already receiving ART. It also confirms the suitability of homoeopathic treatment for HIV/AIDS in resource-limited settings.
APPENDIX 1: KARNOFSKY SCORE
The Karnofsky score runs from 100 to 0, where 100 is ―perfect health and 0 is death. Although practitioners occasionally assign performance scores in between standard intervals of 10, there is no substantiated rationale for this and prognostication is not improved. It seems reasonable to assign the highest score potentially applicable if there is equivocation about a specific case. This scoring system is named after Dr David A. Karnofsky, who described the scale with Dr Joseph H. Burchenal in 1949.
100% – normal, no complaints, no signs of disease
90% – capable of normal activity, few symptoms or signs of disease
80% – normal activity with some difficulty, some symptoms or signs
70% – caring for self, not capable of normal activity or work
60% – requiring some help, can take care of most personal requirements
50% – requires help often, requires frequent medical care
30% – severely disabled, hospital admission indicated but no risk of death
20% – very ill, urgently requiring admission, requires supportive measures or treatment
10% – moribund, rapidly progressive fatal disease processes
0% – death.
APPENDIX 2
SWAZILAND HOMEOPATHY PROJECT MODIFIED KARNOFSKY
PATIENT SCORING SYSTEM
10 (I am well)
Ngiyaphila khakulu
9 . (I feel the problem only a little)
Ngiyawuva umehluko kepha kusesele kancane
8 . (My problem is still there sometimes but not very bad)
Lebengikuva kusekhonyana kepha akusikakhulu noma akusafanani/ngincono kakhulu
7 (I can work but my problem is always there)
Ngingasebenta kepha letimphawu solo tikhona noma tiyevakala/ngincono
6. (The problem makes it difficult for me to work)
Nginebulukhuni bekusebenta kahle ngenca yaloku lengikuvako/nginconywana
5. (I can manage but the problem makes me weak and prevents me from doing the things I need to do)
Ngenca yekungaphili kahle angikhoni kwenta tonkhe tintfo lengidzinga kutentela tona
4. (I am weak and need help to walk)
Ngiphelelwa ngemandla ngidzinga lusito kute ngikhone kuhamba
3. (I am very, very weak)
Sengite emandla kakhulu
2. (I cannot get up or walk)
Angisakhoni kuhamba sengilele phansi
1. (I am very sick and weak ,cannot eat or get up)
Ngiphatseke kakhulu angisakhoni kwenta lutfo - njengekudla nekuvuka 28
APPENDIX 3 – VAS SCALE.
A visual analogue scale (VAS) is a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. When responding to a VAS item, respondents specify their level of agreement to a statement by indicating a position along a continuous line between two end-points. This continuous (or ―analogue) aspect of the scale differentiates it from discrete scales such as the Likert scale.
In practice, computer-analysed VAS responses may be measured using discrete values due to the discrete nature of computer displays
REFERENCES
1. Government of the Kingdom of Swaziland (March 2010). Monitoring the declaration of commitment on HIV/AIDS (UNGASS) Swaziland Country Report.
2. CIA World Factbook (2011). Life Expectancy at Birth.
3. IRIN (2002). World AIDS Day 2002. Swaziland: A long way to go.
4. Physicians for Human Rights (2007). Epidemic of inequality: Women’s Rights and HIV/AIDS in Botswana and Swaziland.
5. Maun Homoeopathy Project (Oct 2005 – July 2008). Pilot Project Independent Evaluation
6. NAM. HIV and AIDS in Practice. Issue 133, March 13, 2010. Peripheral Neuropathy in people with HIV in resource-limited settings.
7. British National Formulary (2007). BMJ Publishing Group Ltd.
8. McDonald. J HN (2009). Handbook of Biological Statistics (2nd edition). Baltimore, Maryland: Sparky House Publishing.
9 Karnofsky DA, Burchenal JH. (1949). The Clinical Evaluation of Chemotherapeutic Agents in Cancer. In: MacLeod CM (Ed), Evaluation of Chemotherapeutic Agents. Columbia Univ Press. 196.
10 Wewers ME & Lowe NK. (1990). A critical review of visual analogue scales in the measurement of clinical phenomena. Research in Nursing and Health 13, 227 – 236.
11 .Medecins Sans Frontiers (November 2010). Fighting a Dual Epidemic. Special Report (Treating Tuberculosis in a high-prevalence HIV setting in rural Swaziland.).