I
I
S
I
MI
M
T
M
We are writing in response to the letter from Soentjens and colleagues; we thank them for their valuable insights. We agree with the comment about serology, and we consider our case a transitioning from acute to chronic infection, and in this context the sensitivity of the serology might indeed be lower than 88%. J Travel Med 2014; 21: 219–221
T
Response to Letter:
M
M
TS
S
S
T
220
Correspondence
We have reviewed the data stored from the urine microscopy slides and some interesting data have come to light. Overall, egg quantity was strikingly low. There were some typical Schistosoma haematobium eggs, together with some other smaller and thinner eggs. At the time of study these atypical eggs were interpreted as infertile eggs (the miracidium was not present or had an aberrant shape). Morphologically they were neither typical Schistosoma bovis nor S. haematobium eggs. When reanalyzing the data in light of the information provided by our colleagues, it is possible that these atypical eggs present in our sample were hybrid (S. haematobium/S. bovis) eggs. The original sample was unfortunately not stored and it is therefore impossible to confirm this finding or perform any more tests. We must point out, however, that S. bovis infections reported in humans are intestinal rather than bladder infections.1 – 3 Thus, we are not certain if these hybrids should also be expected to produce intestinal infection, which was not the case in our patient. On the other hand, we agree that properly designed studies that address the effect of artesunate on Schistosoma worms are lacking. However, we would like to point out to the readers some aspects of our rationale. It is likely that the febrile episode suffered by our patient was Kayatama fever, because it occurred 3 weeks after the first fresh water exposure, a time window that fits with the data published by Grandi`ere-P´erez and colleagues.4 This is a very important conclusion, because the exposure to artemisine took place at this precise moment. Artemisine has been proven to be partially active against juvenile forms of Schistosoma in murine models,5 in which it has drastically reduced the egg burden when given between weeks 4 and 6 postinfection. Some human studies have also indirectly demonstrated a significant reduction in egg burden when artemisine was used in therapeutic doses, both in the acute and chronic phases of infection.6 – 8 Another indirect evidence relies on the low egg burden found in the urine microscopy of our patient (a rigorous egg count was not done). Compared with other Schistosoma cases seen in our center and two related cases of Schistosoma infection (travel companions infected during the same period, who did not receive artesunate), egg quantity was substantially lower. Although there is only one report that has correlated egg burden and serology titers,9 low egg-antigen burden causing seroconversion delay is certainly a biologically plausible explanation; the issue remains open to debate. To summarize, we observed a low quantity of eggs in the urine microscopy. We conclude that this is due to a reduced egg burden which led to the seroconversion delay observed in our patient. We might not be able to clarify if the effect of artemisine on young worms or the possible presence of hybrid Schistosoma species is responsible for the egg burden reduction, but both hypotheses are indeed plausible. The emergence of such
221
Correspondence
hybrid species calls for the development of molecular diagnostics for Schistosoma, which provide an accurate diagnosis in difficult cases such as this.
´ Martínez-Calle, Manuel Rubio, and Nicolas ´ Yuste Jose´ Ramon Division of Infectious Diseases, Clínica Universidad de Navarra, Pamplona, Spain
5.
6.
7.
References 1. Stothard JR, Lockyer AE, Kabatereine NB, et al. Schistosoma bovis in western Uganda. J Helminthol 2004; 78:281–284. 2. Mouchet F, Develoux M, Magasa MB. Schistosoma bovis in human stools in Republic of Niger. Trans R Soc Trop Med Hyg 1988; 82:257. 3. Chunge R, Katsivo M, Kok P, et al. Schistosoma bovis in human stools in Kenya. Trans R Soc Trop Med Hyg 1986; 80:849. 4. Grandi`ere-P´erez L, Ansart S, Paris L, et al. Efficacy of praziquantel during the incubation and invasive phase of
8.
9.
Schistosoma haematobium schistosomiasis in 18 travelers. Am J Trop Med Hyg 2006; 74:814–818. Mahmoud MR, Botros SS. Artemether as adjuvant therapy to praziquantel in murine Egyptian schistosomiasis mansoni. J Parasitol 2005; 91:175–178. Utzinger J, N’Goran EK, N’Dri A, et al. Efficacy of praziquantel against Schistosoma mansoni with particular consideration for intensity of infection. Trop Med Int Health 2000; 5:771–778. Borrmann S, Szlezak N, Faucher JF, et al. Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study. J Infect Dis 2001; 184:1363–1366. Keiser J, N’Guessan NA, Adoubryn KD, et al. Efficacy and safety of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against Schistosoma haematobium: randomized, exploratory open-label trial. Clin Infect Dis 2010; 50:1205–1213. Pinto PL, Kanamura HY, Silva RM, et al. Dot-ELISA for the detection of IgM and IgG antibodies to Schistosoma mansoni worm and egg antigens, associated with egg excretion by patients. Rev Inst Med Trop Sao Paulo 1995; 37:109–115.
J Travel Med 2014; 21: 219–221
I
S
I
MI
M
T
M
We are writing in response to the letter from Soentjens and colleagues; we thank them for their valuable insights. We agree with the comment about serology, and we consider our case a transitioning from acute to chronic infection, and in this context the sensitivity of the serology might indeed be lower than 88%. J Travel Med 2014; 21: 219–221
T
Response to Letter:
M
M
TS
S
S
T
220
Correspondence
We have reviewed the data stored from the urine microscopy slides and some interesting data have come to light. Overall, egg quantity was strikingly low. There were some typical Schistosoma haematobium eggs, together with some other smaller and thinner eggs. At the time of study these atypical eggs were interpreted as infertile eggs (the miracidium was not present or had an aberrant shape). Morphologically they were neither typical Schistosoma bovis nor S. haematobium eggs. When reanalyzing the data in light of the information provided by our colleagues, it is possible that these atypical eggs present in our sample were hybrid (S. haematobium/S. bovis) eggs. The original sample was unfortunately not stored and it is therefore impossible to confirm this finding or perform any more tests. We must point out, however, that S. bovis infections reported in humans are intestinal rather than bladder infections.1 – 3 Thus, we are not certain if these hybrids should also be expected to produce intestinal infection, which was not the case in our patient. On the other hand, we agree that properly designed studies that address the effect of artesunate on Schistosoma worms are lacking. However, we would like to point out to the readers some aspects of our rationale. It is likely that the febrile episode suffered by our patient was Kayatama fever, because it occurred 3 weeks after the first fresh water exposure, a time window that fits with the data published by Grandi`ere-P´erez and colleagues.4 This is a very important conclusion, because the exposure to artemisine took place at this precise moment. Artemisine has been proven to be partially active against juvenile forms of Schistosoma in murine models,5 in which it has drastically reduced the egg burden when given between weeks 4 and 6 postinfection. Some human studies have also indirectly demonstrated a significant reduction in egg burden when artemisine was used in therapeutic doses, both in the acute and chronic phases of infection.6 – 8 Another indirect evidence relies on the low egg burden found in the urine microscopy of our patient (a rigorous egg count was not done). Compared with other Schistosoma cases seen in our center and two related cases of Schistosoma infection (travel companions infected during the same period, who did not receive artesunate), egg quantity was substantially lower. Although there is only one report that has correlated egg burden and serology titers,9 low egg-antigen burden causing seroconversion delay is certainly a biologically plausible explanation; the issue remains open to debate. To summarize, we observed a low quantity of eggs in the urine microscopy. We conclude that this is due to a reduced egg burden which led to the seroconversion delay observed in our patient. We might not be able to clarify if the effect of artemisine on young worms or the possible presence of hybrid Schistosoma species is responsible for the egg burden reduction, but both hypotheses are indeed plausible. The emergence of such
221
Correspondence
hybrid species calls for the development of molecular diagnostics for Schistosoma, which provide an accurate diagnosis in difficult cases such as this.
´ Martínez-Calle, Manuel Rubio, and Nicolas ´ Yuste Jose´ Ramon Division of Infectious Diseases, Clínica Universidad de Navarra, Pamplona, Spain
5.
6.
7.
References 1. Stothard JR, Lockyer AE, Kabatereine NB, et al. Schistosoma bovis in western Uganda. J Helminthol 2004; 78:281–284. 2. Mouchet F, Develoux M, Magasa MB. Schistosoma bovis in human stools in Republic of Niger. Trans R Soc Trop Med Hyg 1988; 82:257. 3. Chunge R, Katsivo M, Kok P, et al. Schistosoma bovis in human stools in Kenya. Trans R Soc Trop Med Hyg 1986; 80:849. 4. Grandi`ere-P´erez L, Ansart S, Paris L, et al. Efficacy of praziquantel during the incubation and invasive phase of
8.
9.
Schistosoma haematobium schistosomiasis in 18 travelers. Am J Trop Med Hyg 2006; 74:814–818. Mahmoud MR, Botros SS. Artemether as adjuvant therapy to praziquantel in murine Egyptian schistosomiasis mansoni. J Parasitol 2005; 91:175–178. Utzinger J, N’Goran EK, N’Dri A, et al. Efficacy of praziquantel against Schistosoma mansoni with particular consideration for intensity of infection. Trop Med Int Health 2000; 5:771–778. Borrmann S, Szlezak N, Faucher JF, et al. Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study. J Infect Dis 2001; 184:1363–1366. Keiser J, N’Guessan NA, Adoubryn KD, et al. Efficacy and safety of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against Schistosoma haematobium: randomized, exploratory open-label trial. Clin Infect Dis 2010; 50:1205–1213. Pinto PL, Kanamura HY, Silva RM, et al. Dot-ELISA for the detection of IgM and IgG antibodies to Schistosoma mansoni worm and egg antigens, associated with egg excretion by patients. Rev Inst Med Trop Sao Paulo 1995; 37:109–115.
J Travel Med 2014; 21: 219–221
