Download File Now

Treatment of Malaria vivax and falciparum with ultraviolet C light via sublingual
application: a clinical report of 3 cases
José Aranda, MD and Martha Villar, MD
Complementary Medicine Treatment center, Department of medicine of Hospital III
(Centro de Atención de Medicina Complementaria, Departamento de Medicina del Hospital III)
Loreto Assistance Network, Health Social Security- EsSALUD, Peru.
( Red Asistencial Loreto, Seguro Social de Salud- EsSalud, Perú)
SUMMARY: Malaria is a public health problem for Peru, where malaria increased fourfold from 1992 to 1997,
and chloroquine and pyrimethamine-sulfadoxine drug-resistant P. falciparum strains have emerged. In light of
these factors, a variation on an old non-pharmacologic treatment was applied in 3 cases. This report
focuses on the clinical presentation and treatment with ultraviolet C light of 3 malaria cases. Two
patients with malaria vivax and one with falciparum decided not to receive the pharmacological
treatment but instead, by their own choice, opted to receive the ultraviolet C light (at a wavelength of
254 nm) sublingually. The disappearance of the symptoms, negative thick drop and the absence of
parasites in the patients that received ultraviolet C light suggests further studies with application of
ultraviolet C sublingually is warranted as a promising therapy for malaria treatment.
KEY WORDS: Malaria vivax, Malaria falciparum, ultraviolet light C, therapeutic use.
INTRODUCTION:
According to the World Health Organization’s 2008 report, an estimated 221,808 cases of Malaria in
Peru resulted in an estimated 128 deaths from the disease in 2006. The pharmacological
treatment plan is unique and free throughout Peru, is guaranteed by the state in all of the health clinics
and establishments, and has been evaluated according to efficiency and efficacy criteria. In
uncomplicated malaria from Plasmodium vivax, the treatment lasts 7 days and efficacy control tests
takes place on the 14th day. In uncomplicated malaria from Plasmodium falciparum, not complicated,
the treatment lasts 3 days and the controls are taken on days 3, 7, and 14, after the beginning of the
treatment (1)
Despite the fact that the drugs play an important role in the control of malaria in Peru and the rest
of the world, the adverse reactions to anti-malaria medications can be frequent (1). Also, the
cross-resistance represents a greater impediment to the development of new anti-malaria
molecules (2). According to Guarda, Asayag and Witzig,
“Clinical resistance of P. falciparum parasites to chloroquine and to the combination
antifolate drug pyrimethamine-sulfadoxine is a growing public health problem in Peru. . .
. Multiple regional in vivo drug susceptibility testing for chloroquine (10% to 70%
resistance) and pyrimethamine-sulfadoxine (10% to 63% resistance) has documented
significant focal differences in resistance patterns” (3)
Given the need to find new alternatives therapies for malaria that can be effective and with little
adverse effects, we evaluated the information on the ultraviolet C light therapy on patients with malaria
Clinical application guides of the Foundation For Blood Irradiation (4) report a number of individual case
studies from the 1940 of patients with malaria successfully treated by exposing a quanta of blood to
ultraviolet light, via the Knott Hemo-irradiator. The method consists in drawing blood from the patient’s
vein, adding an anticoagulant and then passing it through an irradiation chamber, with a maximum
wavelength was 253.7 nm, and then immediately reintroducing it into the patient’s body.
Six cases of malaria induced through malaria-infected blood transfusions, were treated solely with UBI
instead of the pharmacological therapy to end the paroxysm (chills from malaria). Also, it was noted that
a case of malaria acquired normally and treated with UBI resulted in a remission of symptoms (4).
While apparently successful in treating a wide variety of infectious disease processes, the cumbersome
protocol required expertise in handling extracorporeal blood and re-infusion. In light of these hurdles to
widespread application, a novel approach to UV-C exposure was developed utilizing the highly
vascularized sub-lingual mucosa, circumventing the inherent risks of IV access, and extracorporeal biohazards.
Anecdotes and a case study from Africa on file with Harris Medical Resources have suggested the
specific efficacy of sub-lingual UV-C exposure in the remediation of malaria, as well as in a broader array
of infectious diseases. This prompted an investigation of its use in a Peruvian clinical setting. What
follows is a description of three malaria cases treated with ultraviolet C light via sublingual application.
CASE REPORTS
Case 1
The patient entered the malaria program of the Hospital Regional del Ministerio de Salud, Iquitos, Perú,
where she was diagnosed with malaria vivax and was given pharmacological treatment. She has a
history of having acquired malaria vivax 3 times and had exhibited adverse reactions to the anti-malaria
medications. The next day she entered the Centro de Atencion de Medicina Complementaria,
Departamento de Medicina del Hospital III, EsSalud, Iquitos (Center of Attention of Complementary
Medicine, Department of Medicine of Hospital III, Essalud, Iquitos), and stated that she did not want to
take the medication. She was evaluated and presented chills, cephalalgia, general weakness, myalgia
and nausea. About her physical exam: her temperature was 40.6 C, heart rate was 98 heartbeats per
minute, her respiratory rate was 19 breaths per minute, blood pressure was 110/70 mmHg. Her liver
and spleen were not palpable. The peripheral blood revealed a positive thick drop with 5,950 parasites
/ml of blood, anemia (hemoglobin 11.2g/dl), normal leukocytes (5,400/mm3) with 14% of eosinophils
and thrombocytopenia (platelet count, 143,000/mm3). The blood chemistry revealed normal liver
function (AST 8 U/L, ALT 9 U/L, Alkaline Phosphate 150 UI/L, total protein 6.49g/dl, albumin 3.88 g/dl,
globulin 2.61 g/dl, total bilirubin 0.52 mg/dl, indirect bilirubin 0.35 mg/dl) except for the direct bilirubin
0.17 mg/dl which was below the lower limit, creatinine (0.7 mg/dl) and urea (21.8 mg/dl) were normal.
The patient was informed of the experimental therapy with UVC light and later signed the consent form.
She received the UVC light therapy, with a wavelength of 254 nm and an intensity of 800-1200 Uw/cm2,
and emanating from equipment manufactured by the Harris Medical Resources company. The
procedure consisted of administering UVC light sublingually by putting under the patient’s tongue, at
the same time, two cylindrical extremities (2cm in length and 4mm in diameter) attached to the light
guides which are connected to a metallic box that contains the UVC emitting light bulbs. This was
administered for 2 hours a day (1 hour in the morning and one in the afternoon) for 12 consecutive days
and on the 6th day the symptoms disappeared completely. On the 3rd and 7th days the parasitic density
was 4816.6 and 510 parasites/ml respectively. On the 14th day after treatment had begun the thick drop
was negative and the parasitic density 0(Figure 1) and the patient was released. At 21 days after therapy
was started, the patient came in because of a mild cephalalgia, chills and myalgia. Her temperature was
37.9 C and the thick drop was +/2. The parasitic density was 253.3 parasites/mm3 so we returned to the
UVC light therapy, 2 hours a day for 2 days, returning the thick drop to negative and the parasitical load
to 0. The corresponding control on the 28th day was: thick drop, negative, and parasitic density 0.
Biochemical variables after treatment with UVC light: anemia persists (hemoglobin 11g/dl), eosinophils
increase by 29% and the value of platelets and the indirect bilirubin were normalized, the creatinine and
transaminases retained their normal values. We did not use antipyretic pharmaceuticals, only physical
methods. We carried out clinical evaluations of the patient on a monthly basis for 5 months and she did
not show symptoms or signs of the disease.
FIGURE 1. Evolution of the Parasitic Density in a patient with Malaria vivax (Case 1) treated with UVC
light
CASE 2
The patient entered the malaria program of the Hospital Regional del Ministerio de Salud, Iquitos, Perú,
where he was diagnosed with malaria vivax and was given pharmacological treatment. He has a history
of having suffered from malaria 3 times before and has had adverse reactions to the anti-malaria
medications. After 2 days he enters the Centro de Atencion de Medicina Complementaria,
Departamento de Medicina del Hospital III, Iquitos, EsSalud (Center of Attention of Complementary
Medicine, Department of Medicine of Hospital III, Iquitos, EsSalud), and confesses that he has not taken
the medication given to him because of his fear of adverse reactions. During evaluations he presented
chills, cephalalgia, general weakness, myalgia and nausea. The results of his physical exam were:
temperature at 39 C, heart rate was 60 heartbeats per minute, blood pressure was 100/70 mmHg and
his respiratory rate was 23 breaths per minute. Neither liver nor spleen was palpable. The peripheral
blood revealed a positive thick drop for malaria vivax, with 4930 parasites/ml of blood, normal
hemoglobin (14.2g/dl), normal leukocytes (5000/mm3) and thrombocytopenia (platelet count,
32,000/mm3). The patient was informed of the experimental therapy with UVC light and proceeded to
sign the consent form. He was admitted to the hospital and received the UVC light therapy, with a
wavelength of 254 nm and an intensity of 800-1200 Uw/cm2, emanating from equipment manufactured
Harris Medical Resources. The procedure consisted of administering UVC light sublingually by putting
under the patient’s tongue, at the same time, two cylindrical extremities (2cm in length and 4mm in
diameter) attached to the light guides which are connected to a metallic box that contains the UVC
emitting light bulbs. This was administered for 2 hours a day for 5 consecutive days; on the 3rd day of
therapy started to diminish until they disappeared completely. At the 3rd and 7th day after treatment was
begun the parasitic density was 297.5 and 164 parasites/ml respectively. The patient was then released.
In the controls of the 14th and 28th day after therapy was begun his thick drop test was negative and his
parasitical density was 0 (Figure 2). Biochemical variables after treatment with UVC light were: Normal
hemoglobin (12.8g/dl), leukocytes normal (5100/mm3), the platelet count was normal 283,000/mm3.
No antipyretic pharmaceuticals were used, only physical remedies. Clinical evaluations were made
monthly for 5 months and he presented no symptoms or signs of illness.
FIGURE 2. Evolution of the parasitic density of a patient with Malaria vivax (Case 2) treated with UVC
light.
CASE 3
The patient entered the malaria program of the Hospital Regional del Ministerio De Salud, Iquitos, Perú,
where he was diagnosed with malaria falciparum and where he received pharmacological treatment. He
has a history of having suffered from malaria twice before as well as having had adverse reactions to
anti-malaria medications. The next day he entered the Centro de Atención Complementaria ,
Departamento de Medicina del Hospital III, Iquitos, EsSalud (Center of Attention of Complementary
Medicine, Department of Medicine of Hospital III, Iquitos, EsSalud), where he stated that he has not
taken his medications because of side effects. During the evaluation he shows signs of chills, cephalalgia,
myalgia and nausea. At the physical exam the results were as follows: temperature was 39.8C, heart rate
was 92 beats per minute, blood pressure was 110/69 mmHg and the breathing rate was 30 breaths per
minute. The liver and spleen were not palpable. The peripheral blood revealed thick drop for
plasmodium falciparum with 29,665 parasites/ml of blood, and trophozoites, normal hemoglobin
(12.6g/dl), leukocytes normal (4,700/mm3), thrombocytopenia (platelet count, 63,000/mm3). The blood
chemistry revealed an increase in total bilirubin (1.05 mg/dl) and indirect bilirubin (0.54 mg/dl), slight
decrease in albumin level (3.25 g/dl), creatinine is normal (27.7 mg/dl). The patient was informed about
the experimental UVC light therapy and he agreed to sign the consent form, after which he received the
UVC therapy with a frequency of 254nm and with an intensity of 800-1200 Uw/cm2, emanating from the
Harris Medical Resources equipment. The procedure consisted of administering UVC light sublingually by
putting under the patient’s tongue, at the same time, the two cylindrical extremities (2cm in length and
4mm in diameter) at the end of the light guides which are connected to a metallic box that contains the
UVC emitting light bulbs. This therapy was administered for 2 hours a day for 12 consecutive days. The
symptoms disappeared completely on the 6th day of therapy. By the 13th day his thick drop was negative
and his parasitical density was 0 so he was released from the hospital. The initial controls on the 3rd and
7th day were 9,860 and 9,391.5 parasites respectively and the later controls took place on the 14th, 21st,
28th and 35th day after therapy was begun (Figure 3): In all of them the thick drop was negative and the
parasitic density was 0 parasites/ml, 170 parasites/ml, 127.5 parasites/ml and 85 parasites/ml
respectively. The blood biochemistry at the 28th day of control was: anemia (10.9 g/dl), normal
leukocytes (6,100/mm3) with 20% of eosinophils, anisocytosis index 14.8, total bilirubin (1.92 mg/dl),
indirect bilirubin ((1.24 mg/dl) increased. These results indicate jaundice by hemolysis. The increased
alkaline phosphate (375 UI/L) indicates damage to the liver from the inflammatory effects of the
disease. The creatinine, the transaminases, total and fractionated proteins all maintain normal levels.
Results of the control after the 35th day of the start of therapy: the smear reveals granulocytosis, anemia
(19 g/dl) and the anisocytosis continues (14.71); eosinophils 13% (in the absolute differential it is close
to normal), the jaundice by hemolysis is in remission: total bilirubin is normal (0.87 mg/dl) and the
indirect bilirubin (0.53 mg/dl) is close to normal, as is the alkaline phosphate. The rest of the
biochemical variables are normal. We did not use antipyretic pharmaceuticals. We carried out monthly
physical evaluations during a period of 4 months and no symptoms or signs of the disease were present.
FIGURE 3. Evolution of the parasitic density of a patient with Malaria falciparum (Case 3) treated with
UVC light.
DISCUSSION
The physiopathology of malaria results in the destruction of the red blood cells, the release of parasites
and red blood cell material into the blood stream and the reaction of the host to these events. The
plasmodium causes changes to the red blood cells and other organs, producing alterations that could be
light or temporary or that could have serious complications. The release of antigens, pigments and
toxins from the parasite as well as the infected red blood cells and the response of the host give place to
a series of pathological events (5). The severity of the disease is directly proportional to the parasitic
density. The period of incubation is 7 to 14 days for plasmodium falciparum and 8 to 14 days for
vivax (6).
Although the therapeutic method applied to the 3 malaria patients is not exactly the UBI therapy, the
basic principle is the same: the irradiation of the blood using UVC light with a wave length of 254 nm.
For the irradiation of UVC light it was not necessary to extract the patients’ blood since it was delivered
sublingually. The period of illness in all 3 cases was 4 days in average. The three patients were admitted
with the typical malaria symptoms and a definitive diagnosis was verified by a positive thick drop. The 2
cases of malaria vivax showed a low parasitaemia (parasitical density less than 20,000 parasites /ml) and
the falciparum case showed moderate parasitaemia (20,000 to 50,000 parasites /ml). In the case of
malaria falciparum the symptoms were more intense. The first case had anemia, which persisted until
the last control, while the third case, where at the beginning the hemoglobin was normal the last
controls showed anemia as well. The three patients showed evidence of Thrombocytopenia, but in cases
2 and 3 the reduction was more significant. From the beginning the case of malaria falciparum shows
biochemical alterations compatible with an icteric by hemolysis (total bilirubin 1.05 mg/dl and indirect
bilirubin 0.54 mg/dl, increased). These values in the 28th day control increased more, but their
normalization was achieved on the 35th day control. This data correlates with the evolution of the illness.
The alkalyne phosphatase levels also increased which can be explained by the inflammatory process of
malaria but those too returned to normal.
The decision of how long to apply the UVC therapy depended on the moment when the thick drop came
back negative and the parasitic load was reduced to 0. That is why cases 1 and 3 received 12 days of
continuous therapy and in both cases the symptoms disappeared completely on the 6th day. The
progressive reduction of the parasitic density in the 3 cases can be seen in Figures 1, 2 and 3, possibly as
an effect of the UVC light, although in the first case, on the 21st day, there was a recurrence or reinfection. On the 14th control day the three cases presented negative thick drops and a parasitical
density of 0. On the 28th day of control the 2 cases of malaria vivax presented negative thick drop and a
parasitic density of 0 while the falciparum case showed a negative thick drop and a parasitic density of
127 parasites /ml. As far as the platelet count, the normal values were achieved. It is important to
mention that on the 28th day, an intense eosinophilia was noted in cases 1 and 3, possibly because of a
parasitosis.
Considering the apparent efficacy of sub-lingual UV-C in treating a variety of infectious diseases, viral,
fungal, bacterial and parasitic, it has been suggested that its effect is indirect, and mediated by
modulation of the host immune system. This is also suggested in our cases by the up-regulation of
eosinophil activity, commonly associated with parasitic infections, and post-acute phase malaria (8).
CONCLUSION
While the evidence for the application of UV-C irradiation in the treatment of malaria remains in the
stage of anecdotes and individual case studies, the reproducible results in the 3 cases presented remains
encouraging, and warranting of further controlled studies. In light of multiple-drug resistant strains of
malaria now encountered by clinicians, and the increasing toxicity and side-effect profiles of stronger
pharmacological agents, it seems imperative that alternative, non-pharmacological agents be
investigated as well. Sub-lingual UV-C irradiation shows potential for being one of those tools in the fight
against this endemic disease in Peru.
BIBLIOGRAPHICAL REFERENCES
1. Norma Técnica para la Atención Curativa de la Malaria. Nuevos Esquemas Terapeúticos en el
Tratamiento de la Malaria en el Perú. Directiva N° 005-2001-DGSP-DEAIS-DPCRD-PCMOEM,
21
2. Yeramin P. et al. Efficacy of DB289 in Thai patients with Plasmodium vivax or acute,
uncomplicated Plasmodium falciparum infections. Brief report. 2005(15): 319-322
3. Javier Aramburú Guarda, César Ramal Asayag, and Richard Witzig. Malaria Reemergence in
the Peruvian Amazon Region, Emerging Infectious Diseases, Vol. 5, No. 2, April.June 1999
4.
Miley G P, Olney R C, Lewis HT. Ultraviolet Blood Irradiation: A History and Guide to Clinical
Application(1933-1997). Silver Spring, Maryland: Foundation for Blood Irradiation, Inc 1997. 1112,225,226
5. Angulo V , Tarazona Z, Vega A, Velez I, Betancurt J. Leishmaniosis, Chagas y Malaria: Guias
de Práctica Clínica Basada en la Evidencia.Proyecto ISS-ASCOFAME. 9-10
6. Organización Panamericana de la Salud. Manual de Diagnóstico y Tratamiento en
Especialidades Clínicas: Enfermedades Infecciosas. OPS, 2003. 330-331
7. Rojas W. Inmunologia. Corporación para la Investigación Biológica( CIB). 13 ava ed. 420
8. J A L Kurtzhals, et al. Increased eosinophil activity in acute Plasmodium falciparum
infection—association with cerebral malaria, Clin Exp Immunol. 1998 May; 112(2): 303–
307.