Efficacy and tolerability of a low-dose mefloquine-sulfadoxine-pyrimethamine combination compared with chloroquine in the treatment of acute malaria infection in a population with multiple drug-resistant Plasmodium falciparum.

The efficacy and tolerability of single, low-dose mefloquine, sulfadoxine-pyrimethamine (MSP) combination was compared with chloroquine (CQ) for malaria treatment in a malaria-endemic area of Nigeria with multiple drug-resistant Plasmodium falciparum. The two drug regimens (MSP and CQ) were tested in a 12-month prospective population study. The patients were divided into two groups. Group 1 patients were treated presumptively, based on malaria symptoms. Group 2 patients were treated based on a parasitologic diagnosis using the World Health Organization seven-day in vivo test and extended to a 28-day follow-up period. Tolerability was assessed by the incidence and intensity of adverse events. One thousand nine hundred thirty-five patients visiting 10 health facilities, including the University of Calabar Teaching Hospital, were enrolled. The study showed that the low-dose MSP was efficacious, with day 7 response rates of 95% and 91% for (presumptive) Group 1 and (in vivo) Group 2, respectively, while CQ had day 7 response rates of 82% and 66% in Groups 1 and 2, respectively. The low-dose MSP was significantly (P < 0.0001) more efficacious, with faster fever and parasite clearance times than CQ in this area of CQ-resistant P. falciparum malaria. Eight patients treated with CQ, including seven severe cases (RII-RIII) were successfully re-treated with MSP. Adverse events were generally more common among those treated with MSP (29%) than those treated with CQ (17%). However, the adverse events caused by both drugs were mild to moderate and self-limited. The MSP combination appears to be a good substitute for CQ, in view of multiple drug resistance, especially in areas with severe (RII-RIII) malaria.

Correlation between in vivo and in vitro response of chloroquine-resistant Plasmodium falciparum in Calabar, south-eastern Nigeria.

Since chloroquine-resistant Plasmodium falciparum (CRPF) has emerged in Nigeria, we monitored the susceptibility of the parasite strain to a standard chloroquine (C25) dose in our Children's Emergency Unit. Chloroquine (CQ) is the drug of choice for malaria chemotherapy in Nigeria. The WHO 7-day in vivo evaluation and Rieckmann's microtitre technique (in vitro test) were used. 33 children of mean age 4.9 years were enrolled in the study. 27 (81.8%) of the in vitro cultures were successful. 16 (59.3%) of the successful isolates still showed schizogony at CQ concentration of 5.7 pmol/well and above. 28 (84.8%) of the children completed the in vivo study. 15 (53.6%) were parasitaemic on day 7 and/or day 14 and were regarded as parasitologic failures. The isolates from 14 of these children showed corresponding in vitro resistance of CQ concentrations equal to or above 5.7 pmol/well. The proportion of RIII (= 13.3%) appears to have increased as compared to 5.9% recorded in 1987. We conclude that there appears to be a good correlation between in vivo evaluation of parasitologic failures (53.6%) and in vitro resistance (59.3%). It thus appears that CRPF is definitely increasing in South-Eastern Nigeria. This can be expected not only to complicate malaria chemotherapy in the Children's Emergency Unit of the University of Calabar Teaching Hospital, but will contribute immensely to the deterioration of malaria therapy and control in Nigeria.

IgG2 associated hypergammaglobulinaemia in some Nigerians with HIV infection.

Concentrations of immunoglobulins (IgA, IgG and IgM) were measured in Nigerians with (HIV) infection. Considerable elevations up to two-fold the reference values were observed for IgG and IgM in the patient group as a whole but elevations in IgA concentration were least marked albeit significantly different from the healthy subjects. Elevation of a particular isotype was not always concomitant with elevation of the other major classes in the same patient. Overall, these elevations were observed in both symptomatic and asymptomatic infected subjects. Further analysis of IgG hyperglobulinemia showed that increases in this major class may be due to increased IgG2 subclass concentrations. It is suggested that elevation of IgG2 subclass in Nigerians with HIV infection and not IgG1 or IgG3 may be due to genetic and environmental factors rather than variation in the strain of the virus.

PIP: The major and subclass concentrations of immunoglobulins were examined in 27 Nigerians with HIV infection. 12 had definite HIV-1 infection, 2 had both HIV-1 and HIV-2, and the remaining 15 were included because of the reactivity of their sera. The reference group was drawn from four major Nigerian population groups that were part of a group of 238 healthy Nigerians. Individual increases in IgM and IgG concentrations in the patient group varied and was sometimes up to 7-fold above the mean of those in the control group. Overall, the increases were about twice the mean concentrations found in the reference group. The IgM concentration range was 0.6-9.7 g/l in the HIV group (n = 27) vs. 0.4-4.6 in the reference group (n = 157, p 0.02). The IgG concentration range was 10-70 g/l in the HIV group (n = 27) vs. 10-30 g/l in the reference group (n = 160, p .001). The highest IgG concentrations in cases were found in symptomatic patients, but this relationship was not observed for IgM and IgA. The scattergram of IgA concentrations was the least elevated. The increase was significant when those with HIV-1 infection alone were compared with the healthy subjects (p .05). IgG2 subclass concentrations were determined only in patients of Kanuri and Hausa populations. In comparison to their healthy counterparts, IgG2 concentrations were significantly higher in the patient group (p .001). Other IgG subclasses showed a bimodal distribution in both groups. There was no significant difference in distribution of IgG1, IgG3, and IgG4 concentrations between the reference and the HIV groups. In several ethnic groups polyclonal hypergammaglobulinemia has been reported to be a frequent feature of HIV infection with markedly increased IgA concentrations. The differences observed here do not reflect a variation in the strain of the virus in the Nigerian populations, but may be related to racial and environmental factors.

Serum C-reactive protein and C3 complement protein levels in severely malnourished Nigerian children with and without bacterial infections.

Bacterial infections are the major determinants of fatality in severe protein-energy malnutrition (PEM). Unfortunately, these infections are difficult to diagnose clinically. C-reactive protein (CRP) levels were determined in 17 infected and 10 non-infected Nigerian children with severe PEM and compared with age/sex-matched apparently healthy controls. The aim was to study the response of this acute phase protein to bacterial infections as well as to assess its value in the diagnosis of infections in severe PEM. C3 complement protein levels were also determined in the same group of subjects. The major organisms isolated in samples from these subjects were S. aureus and the coliforms. Mean CRP level in the non-infected children with severe PEM was 13.8 +/- 6.21 mg/l and rose to 159.83 +/- 124.07 mg/l in the presence of infection. The mean value in healthy non-infected controls was 2.01 +/- 0.96 mg/l. The difference in the mean CRP levels between the infected and non-infected PEM children was statistically significant at p < 0.01. The mean difference between the non-infected and the control subjects was not significant. Using a diagnostic level of 20.00 mg/l of CRP gave a sensitivity of 85.0% and a specificity of 80.0%. This CRP level is a useful index of bacterial infections in severe PEM. C3 complement protein was low in the non-infected malnourished group, but rose significantly in the presence of infection to values similar to that of the healthy controls. C3 protein thus behaves as an acute phase reactant in the presence of infection in severe PEM, and does not appear to be consumed, probably due to a deficiency in the early components of the complement cascade. This suggests a role for C3 measurement in the monitoring of bacterial infections in severe PEM.

Serum complement levels in asymptomatic Plasmodium falciparum parasitaemic children.

Twenty-eight (42%) of 67 afebrile children (mean age 6.3 +/- 3.6 years) undergoing various minor elective surgeries were slide positive for malaria parasitaemia. All infected subjects were given oral chloroquine therapy before and after blood samples were collected. Pre- and post-treatment complement (C4, C3, Bf and CH50 levels were evaluated in 15 of the subjects who had parasite densities > or = 500/microliter. These were compared with the levels in 15 age/sex-matched children who had acute malaria, as well as with the levels in 15 age/sex matched, non-infected controls. Significant consumption of C4 was observed in both the asymptomatic (p < 0.05) and symptomatic (p < 0.05) subjects. The mean serum levels of C4 were significantly higher in the asymptomatic, when compared with the symptomatic subjects (p < 0.01), and the healthy controls (p < 0.05). The distribution of classical pathway complement haemolytic titres in the groups studied was the same as that of the C4 levels. It is concluded that the forth component of the classical complement pathway may play a protective role in asymptomatic malaria.